Cardiac Enlargement Research Articles

Cardiac Enlargement in a Medicolegal Autopsy Setting.

A key element for diagnosing cardiac enlargement in an autopsy setting is relevant heart weight references. However, most available references are to a large extent not representative of a medicolegal autopsy population, implying that reference weights are likely lower than those in the relevant population.To establish more applicable heart weight references in a medicolegal autopsy population, we designed a heart weight model that accounts for undiagnosed cardiac enlargement using data from 11,897 nontraumatic Swedish medicolegal autopsy cases autopsied between 2010 and 2019. The model was validated in 296 nonobese young adult suicidal hanging cases.For a decedent of average height (174 cm), the evidence that a heart weight was enlarged reached weak support at approximately 430 g, substantial support at approximately 480 g, and strong support at 520 g. The modeled prevalence of cardiac enlargement was very high among elderly and obese decedents.We believe that our model is more applicable in a medicolegal setting than those previously published. The presented quantification of the degree of uncertainty regarding diagnosis can help the pathologist in diagnosing cardiac enlargement. To facilitate the use of this model, we also made it available through a simple online tool ( https://formedum.shinyapps.io/HeartWeightCalc/ ).

THU660 Pericardial Effusion Secondary To Uncontrolled Hypothyroidism

Abstract Disclosure: G.D. Cain: None. D. Goldsmith: None. E. Ruel: None. Introduction: Hypothyroidism is an endocrine disorder that can effect multiple organ systems. Pericardial effusion is a rare but significant complication of hypothyroidism. Early diagnosis and management of the pericardial effusion is important to prevent progression to cardiac tamponade and hemodynamic instability. We present a case of pericardial effusion in a 62-year-old female with hypothyroidism and medication non-compliance. Case Presentation: A 62-year-old female with past medical history of hypothyroidism and hypertension presented to the emergency department due to altered mental status. Patient's family reported that she had a progressive decline in her speech for more than a month, until she became completely aphasic on day of presentation, which prompted them to call EMS. Patient had diminished exercise capacity, dyspnea on exertion, bilateral pedal edema over the past couple of months. Family also reported that the patient had been depressed and negligent of her health following the passing of her husband three years ago. She was not taking her medications including levothyroxine. In the ED, patient was hypertensive, blood pressure was 190/100. CT head stroke protocol did not show stroke. Chest x-ray showed massive cardiac enlargement. 2D-Echo confirmed a large pericardial effusion without cardiac tamponade. Thyroid function panel showed high TSH of 77, free T4 was undetectable. Pericardial effusion was most likely secondary to hypothyroidism. Myxedema coma was suspected due to patient's progressive mental deterioration. Patient also had myxedema of bilateral lower extremities. IV levothyroxine and hydrocortisone were started with improvement in her symptoms. A pericardial window was performed by the thoracic surgeon for her large pericardial effusion. Patient had large amounts of drainage from JP pericardial drain for more than two weeks following the surgery. JP drain was removed after the amount of drainage decreased to less than 100 ml a day. Cultures and cytology for malignancy were sent and all came back negative. Patient’s symptoms improved with treatment and the she was discharged on levothyroxine 137 mcg daily. Patient was counseled to take her medication regularly. Follow-up appointments were arranged with primary care provider and endocrinology. Discussion: Pericardial effusion is a rare complication of hypothyroidism, more likely to be seen in severe, untreated hypothyroidism such as in this case. The mechanism of pericardial effusion in hypothyroidism is through increased capillary permeability in heart and decreased lymphatic drainage of albumin, resulting in accumulation of fluid in the pericardial space. The effusion develops over time and patients can have large amounts of volume at the time of diagnosis without tamponade physiology. Early diagnosis is important to avoid tamponade and hemodynamic instability. Presentation: Thursday, June 15, 2023

M-Mode Echocardiography in Canine Veterinary Practice: A Comprehensive Review of Left Ventricular Measurements in 44 Different Dog Breeds.

This review article focuses on the use of canine M-mode in veterinary medicine, specifically in assessing the left ventricle measurements in several breeds. It traces the historical development of echocardiography techniques, including A-mode, B-mode, and motion mode (M-mode), which provide accurate unidimensional records of cardiac structures. This article highlights the significance of M-mode measurements in diagnosing stage B2 of MMVD, where left ventricular end-diastolic internal diameter corrected with body weight (LVIDdN) is essential for identifying cardiac enlargement. It also explains the role of M-mode in diagnosing DCM, outlining criteria such as left ventricular dilatation. The authors emphasize the importance of breed-specific reference values for echocardiographic measurements due to variations in somatotype among dogs. This review provides a comprehensive table summarizing M-mode measurements of the left ventricle for 44 different dog breeds, including interventricular septum thickness, left ventricular internal diameter, and left ventricular posterior wall thickness during systole and diastole. This review's methodology involves compiling data from various scientific literature sources, providing an extensive tabular representation of M-mode measurements for different breeds, ages, and sexes. Overall, this review highlights the critical role of M-mode echocardiography in diagnosing and managing cardiac diseases in dogs, underscores the importance of breed-specific reference values, and presents a comprehensive summary of M-mode measurements for various dog breeds, aiding both clinicians and researchers.

Identification of membrane palmitoylated protein 1 (MPP1) as a heart-failure-promoting protein triggered by cardiovascular risk factors and aging

Membrane-Associated Guanylate Kinase (MAGUK) proteins are scaffold proteins with well-established functions in the neuronal system. A role of MAGUK protein up-regulation in the pathogenesis of heart failure is not established. This study identified the up-regulation of the MAGUK family protein MPP1 (Membrane Palmitoylated Protein 1), in cardiac transcriptome data of three different heart failure models. MPP1 was up-regulated in failing hearts of B6 mice with long-term chronic pressure overload, in failing hearts of aged Apoe−/− mice with long-term atherosclerosis, and in failing hearts of RKIP-transgenic mice with cardiotoxic lipid overload. MPP1-transgenic mice revealed that moderately (2-fold) increased cardiac MPP1 levels caused symptoms of heart failure with a significantly reduced left ventricular ejection fraction of 39.0 ± 6.9 % in Tg-MPP1 mice compared to 55.2 ± 3.7 % of non-transgenic B6 controls. Echocardiographic and histological analyses detected cardiac enlargement and cardiac dilation in Tg-MPP1 mice. The angiotensin II AT1 receptor (AGTR1) and MPP1 were co-localized on sarcolemmal membranes in vivo, and Tg-MPP1 mice had increased levels of cardiac AGTR1, which has an established heart failure-promoting function. The increased AGTR1 protein could be directly triggered by elevated MPP1 because MPP1 also increased the AGTR1 protein in non-cardiomyocyte HEK cells, which was detected by fluorescence measurement of AGTR1eYFP. MPP1 was not only up-regulated by major cardiovascular risk factors but also by old age, which is a major contributor to heart failure. Thus, the aging-induced MPP1 exerts a previously unrecognized role in heart failure pathogenesis by upregulation of the angiotensin II AT1 receptor (AGTR1) protein.

The Thoracic Inlet Length as a Reference Point to Radiographically Assess Cardiac Enlargement in Dogs with Myxomatous Mitral Valve Disease.

The diagnostic value of the vertebral heart size (VHS) in dogs with mitral valve degeneration (MVD) is compromised when middle thoracic vertebral anomalies are present. The objective of this study was to assess the use of the thoracic inlet heart score (TIHS) to identify left heart enlargement (LHE) secondary to MVD. The cardiac silhouette of 50 clinically healthy dogs and 106 MVD dogs in different stages was assessed on a right lateral chest radiograph. The TIHS and VHS value were calculated for each patient and compared. The TIHS was significantly different between the control dogs and the dogs with MMVD, increasing with disease stage, control 2.91 ± 0.23, Stage B1 2.98 ± 0.36, B2 3.25 ± 0.34, and C 3.53 ± 0.36, p < 0.05. A THIS ≥3.3 showed 69% sensitivity and 81% specificity to identify LHE. The TIHS showed moderate correlation with the VHS, LA/Ao, and LVIDDN 0.59, 0.42, and 0.62, respectively. The intraobserver and interobserver agreement were almost perfect, 0.96, and substantial, 0.73. The TIHS method can be used to identify LHE secondary to MMVD on dogs' thoracic radiographs.

Effectiveness of Halo-Pelvic Traction and Thoracoplasty for Pulmonary Artery Pressure and Cardiopulmonary Function in Patients With Severe Spinal Deformity.

Retrospective review. To evaluate the effectiveness of halo-pelvic traction and thoracoplasty for pulmonary artery pressure (PAP) and cardiopulmonary function in patients with severe spinal deformity. The effect of severe spinal deformity on pulmonary arterial hypertension, cardiac structure, and function has received little attention before. A total of 21 patients with severe spinal deformity were included in our study; all patients were examined by echocardiography and pulmonary function test before and after treatment. The correlations between PAP and pulmonary function were examined using Pearson correlation analysis. The PAP decreased from 58.67 ± 20.24 to 39.00 ± 12.51 mm Hg, and the PAP of 42.86% of the patients returned to normal after treatment. Right cardiac enlargement, left ventricular diastolic function, and pulmonary function were improved at the same time. The ratio of left ventricular to right ventricular diameter returned to normal. Moderate correlations (correlation coefficient: -0.513 to -0.559) between PAP and forced vital capacity and forced expiratory volume in the first second were identified. Pulmonary arterial hypertension, ventricular diastolic function, and pulmonary function were improved after halo-pelvic traction and thoracoplasty. A moderate negative correlation was identified between PAP and pulmonary function: the more pulmonary function improved, the more PAP decreased.

Parallels between oncogene-driven cardiac hyperplasia and heart regeneration in zebrafish.

The human heart is poorly regenerative and cardiac tumors are extremely rare. Whether the adult zebrafish myocardium is responsive to oncogene overexpression and how this condition affects its intrinsic regenerative capacity remains unknown. Here, we have established a strategy of inducible and reversible expression of HRASG12V in zebrafish cardiomyocytes. This approach stimulated a hyperplastic cardiac enlargement within 16 days. The phenotype was suppressed by rapamycin-mediated inhibition of TOR signaling. As TOR signaling is also required for heart restoration after cryoinjury, we compared transcriptomes of hyperplastic and regenerating ventricles. Both conditions were associated with upregulation of cardiomyocyte dedifferentiation and proliferation factors, as well as with similar microenvironmental responses, such as deposition of nonfibrillar Collagen XII and recruitment of immune cells. Among the differentially expressed genes, many proteasome and cell-cycle regulators were upregulated only in oncogene-expressing hearts. Preconditioning of the heart with short-term oncogene expression accelerated cardiac regeneration after cryoinjury, revealing a beneficial synergism between both programs. Identification of the molecular bases underlying the interplay between detrimental hyperplasia and advantageous regeneration provides new insights into cardiac plasticity in adult zebrafish.

The cardiothoracic ratio in postmortem chest radiography: Reliability and threshold to predict cardiomegaly

The cardiothoracic ratio (CTR) is a useful technique to investigate the prevalence of cardiomegaly, an important clinical manifestation of several cardiovascular diseases. The aim of this study was to determine the relationship between various macroscopic measurements of heart size on postmortem chest X-rays and CTR as well as develop a new CTR threshold or scoring system to improve reliability of CTR in forensic settings. We selected 131 forensic autopsy cases aged more than 18. The heart length and width, wall thicknesses, chamber diameters, and heart weights were measured during autopsy. The postmortem CTR was measured in an anteroposterior chest radiography. In autopsy cases among the Thai population, two groups were defined: normal and overweight heart, with cut-off values based on average heart weight + 1SD. The results showed that the wall thickness and chamber diameter were not related to CTR, but the heart length and width were. A multivariable analysis was performed and showed good discriminating power, with an area under the ROC curve of 0.88. A new formula was developed, which included age, BMI, and CTR. The recommend cut-off score was 122 for the diagnosis of cardiomegaly, in which the sensitivity and specificity were 78.3% and 72.9%. The findings of increased CTR cannot be equated to cardiac wall hypertrophy and chamber enlargement. This study suggests that a combination of CTR, BMI, and age of the deceased improves the level of discrimination between the condition of normal heart and cardiomegaly before autopsy.

Therapeutic targeting of vascular malformation in a zebrafish model of hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) causes arteriovenous malformations (AVMs) in multiple organs to cause bleeding, neurological and other complications. HHT is caused by mutations in the BMP co-receptor endoglin. We characterised a range of vascular phenotypes in embryonic and adult endoglin mutant zebrafish and the effect of inhibiting different pathways downstream of Vegf signalling. Adult endoglin mutant zebrafish developed skin AVMs, retinal vascular abnormalities and cardiac enlargement. Embryonic endoglin mutants developed an enlarged basilar artery (similar to the previously described enlarged aorta and cardinal vein) and larger numbers of endothelial membrane cysts (kugeln) on cerebral vessels. Vegf inhibition prevented these embryonic phenotypes, leading us to investigate specific Vegf signalling pathways. Inhibiting mTOR or MEK pathways prevented abnormal trunk and cerebral vasculature phenotypes, whereas inhibiting Nos or Mapk pathways had no effect. Combined subtherapeutic mTOR and MEK inhibition prevented vascular abnormalities, confirming synergy between these pathways in HHT. These results indicate that the HHT-like phenotype in zebrafish endoglin mutants can be mitigated through modulation of Vegf signalling. Combined low-dose MEK and mTOR pathway inhibition could represent a novel therapeutic strategy in HHT.

Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy

Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. CCC is characterized by parasite persistence and inflammatory response in the heart tissue, which occur parallel to microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling in the cardiac tissue of chronically T. cruzi-infected mice treated with a suboptimal dose of benznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of both (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX treatment regimens improved electrocardiographic alterations, reducing the percentage of mice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when compared with the vehicle-treated animals. miRNA Transcriptome profiling revealed considerable changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment groups compared with the control (infected, vehicle-treated) group. The latter showed pathways related to organismal abnormalities, cellular development, skeletal muscle development, cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice exhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle, cell death and survival, tissue morphology, and connective tissue function. Finally, the Bz+PTX-treated group revealed 58 differentially expressed miRNAs associated with key signaling pathways related to cellular growth and proliferation, tissue development, cardiac fibrosis, damage, and necrosis/cell death. The T. cruzi-induced upregulation of miR-146b-5p, previously shown in acutely infected mice and in vitro T. cruzi-infected cardiomyocytes, was reversed upon Bz and Bz+PTX treatment regimens when further experimentally validated. Our results further our understanding of molecular pathways related to CCC progression and evaluation of treatment response. Moreover, the differentially expressed miRNAs may serve as drug targets, associated molecular therapy, or biomarkers of treatment outcomes.

Effects of ketamine-induced H3K9 hypoacetylation during pregnancy on cardiogenesis of mouse offspring.

Prenatal exposure to adverse factors can cause congenital heart defects. Ketamine, a widely used anesthetic drug, produces several adverse reactions such as tachycardia, hypertension, and laryngospasm, especially in pediatric patients. This study aimed to detect the effects of ketamine exposure during pregnancy on the cardiogenesis of mouse offspring and the potential mechanisms. In this study, ketamine at an addictive dose (5mg/kg) was administered to mice during early gestation to explore the epigenetic mechanism of its causing cardiac dysplasia. The cardiac morphology of the mouse offspring was observed through hematoxylin-eosin staining and transmission electron microscopy. The heart function of one-month-old neonates was detected by echocardiography. The expression of cardiomyogenesis-related genes was detected by western blot and RT-qPCR. The acetylation level of histone H3K9 at the Mlc2 promoter and its deacetylase level and activity were detected by CHIP-qPCR, RT-qPCR, and ELISA, respectively. Our data revealed that ketamine exposure during pregnancy could cause cardiac enlargement, myocardial sarcomere disorganization, and decreased cardiac contractile function in mouse offspring. Moreover, ketamine reduced the expression of Myh6, Myh7, Mlc2, Mef2c, and cTnI. The histone H3K9 acetylation level at the Mlc2 promoter was down-regulated by increasing the histone deacetylase activity and HDAC3 level upon ketamine administration. Our work indicates that H3K9 acetylation is a vital player in cardiac dysplasia in offspring caused by prenatal ketamine exposure and HDAC3 is a key regulatory factor.

Galangin alleviated myocardial ischemia-reperfusion injury by enhancing autophagic flux and inhibiting inflammation

Autophagy is critically involved in myocardial ischemia-reperfusion (I/R). Autophagy inhibition exacerbates myocardial I/R injury. Few effective agents target autophagy to prevent myocardial I/R injury. Effective drugs that promote autophagy in myocardial I/R warrant further investigation. Galangin (Gal) enhances autophagy and alleviates I/R injury. Here we conducted both in vivo and in vitro experiments to observe the changes in autophagy after galangin treatment and investigated the cardioprotective effects of galangin on myocardial I/R. MethodsAfter 45-min occlusion of the left anterior descending coronary artery, myocardial I/R was induced by slipknot release. One day before surgery and immediately after surgery, the mice were injected intraperitoneally with the same volume of saline or Gal. The effects of Gal were evaluated using echocardiography, 2,3,5-triphenyltetrazolium chloride staining (TTC staining), western blotting, and transmission electron microscopy. Primary cardiomyocytes and bone marrow–derived macrophages were extracted in vitro to measure the cardioprotective effects of Gal. ResultsCompared with the saline-treated group, Gal significantly improved cardiac function and limited infarct enlargement after myocardial I/R. In vivo and in vitro studies demonstrated that Gal treatment promoted autophagy during myocardial I/R. The anti-inflammatory effects of Gal were validated in bone marrow–derived macrophages. These results strongly suggest that Gal treatment can attenuate myocardial I/R injury. ConclusionOur data demonstrated that Gal could improve left ventricular ejection fraction and reduce infarct size after myocardial I/R by promoting autophagy and inhibiting inflammation.

The role of alpha actinin paralogs in cardiac hypertrophy and contractile force production.

Sarcomeres are the basic contractile unit within heart muscle cells (cardiac myocytes) that drive each heartbeat. New sarcomere formation (sarcomerogenesis) is concomitant with cardiac myocytes enlargement and is associated with physiological heart growth and cardiomyopathies. A detailed understanding of sarcomerogenesis is of high interest as it would inform our knowledge of both normal and pathological heart biology. Each sarcomere is bordered by Z-lines which mechanically link adjacent sarcomeres within myofibrils to transmit the forces of contraction. A key structural protein at Z-lines is the muscle-specific actin filament bundler, α-actinin 2. Depletion of α-actinin 2 from cardiac myocytes disrupts sarcomerogenesis, but nothing is known about the roles of other α-actinin paralogs. α-actinin 4—sometimes called a “non-muscle” paralog—is expressed in cardiac myocytes ∼30 fold lower than α-actinin 2. Using an assay we developed using cultured iPSC-derived cardiac myocytes, we show that α-actinin 4 colocalizes with α-actinin 2 both in the precursors of sarcomeres as well as within the Z lines of sarcomeres. Unlike the loss of sarcomeres due to the depletion of α-actinin 2, depletion of α-actinin 4 resulted in larger cardiac myocytes with more sarcomeres. Our data indicates that this is due to a stabilization of α-actinin 2. We hypothesized that depletion of α-actinin 4 in vivo would result in an enlargement of the heart. Therefore, we depleted α-actinin 4 from zebrafish embryos. Zebrafish have a two chambered heart, which consists of an atrium and ventricle. To our surprise, only the atrium was significantly enlarged. Ongoing work is suggestive of a mechanism in which the presence of α-actinin 4 within cardiac myocytes of the atrium reduces the number, size, and force producing capabilities of sarcomeres. This mechanism could explain why the atrium is physically weaker than the ventricle.

Intracardiac paraganglioma with a cough as the first symptom

BackgroundCardiac paragangliomas (PGLs) are clinically rare, with hypertension and metabolic changes as the main symptoms. The tumor is highly related to gene mutation, and surgery is presently the effective treatment. Medical history and clinical manifestations of the patient, routine laboratory examinations and imaging examinations, and pathological examination can help the final diagnosis.Case presentationThe present study presents a 31-year-old male patient with a left atrial mass. The initial symptom was cough. Cardiac enlargement was found during the chest X-ray. The follow-up imaging examination revealed a left atrial occupying lesion, and the possibility of malignant occupying lesions was not ruled out. The patient underwent surgical resection of the mass. The final pathological result revealed paraganglioma. The thoracic computed tomography review two months after the operation revealed that the original occupying lesion disappeared, and no new lesion was found.ConclusionsPheochromocytomas and paragangliomas (PPGLs) are a kind of neuroendocrine tumors. PPGLs can cause secondary hypertension, and lead to a series of clinical syndromes, including myocardial injury, metabolic changes, and so on. The occurrence of PPGIs is related to gene mutation. Biochemical detection, imaging examination, and genetic testing can help diagnose. The tumor should be surgically removed as soon as possible after the diagnosis. As a functional tumor, PPGLs should be fully prepared before surgery to avoid anesthesia and huge fluctuations in blood pressure during and after surgery, or the occurrence of fatal hypertensive crisis and intractable hypotension after tumor resection. Adequate preoperative preparation directly affects the prognosis of patients after surgery. Therefore, multidisciplinary cooperation before, during, and after the operation is extremely important.

Knockout of the Complex III subunit Uqcrh causes bioenergetic impairment and cardiac contractile dysfunction

Ubiquinol cytochrome c reductase hinge protein (UQCRH) is required for the electron transfer between cytochrome c1 and c of the mitochondrial cytochrome bc1 Complex (CIII). A two-exon deletion in the human UQCRH gene has recently been identified as the cause for a rare familial mitochondrial disorder. Deletion of the corresponding gene in the mouse (Uqcrh-KO) resulted in striking biochemical and clinical similarities including impairment of CIII, failure to thrive, elevated blood glucose levels, and early death. Here, we set out to test how global ablation of the murine Uqcrh affects cardiac morphology and contractility, and bioenergetics. Hearts from Uqcrh-KO mutant mice appeared macroscopically considerably smaller compared to wildtype littermate controls despite similar geometries as confirmed by transthoracic echocardiography (TTE). Relating TTE-assessed heart to body mass revealed the development of subtle cardiac enlargement, but histopathological analysis showed no excess collagen deposition. Nonetheless, Uqcrh-KO hearts developed pronounced contractile dysfunction. To assess mitochondrial functions, we used the high-resolution respirometer NextGen-O2k allowing measurement of mitochondrial respiratory capacity through the electron transfer system (ETS) simultaneously with the redox state of ETS-reactive coenzyme Q (Q), or production of reactive oxygen species (ROS). Compared to wildtype littermate controls, we found decreased mitochondrial respiratory capacity and more reduced Q in Uqcrh-KO, indicative for an impaired ETS. Yet, mitochondrial ROS production was not generally increased. Taken together, our data suggest that Uqcrh-KO leads to cardiac contractile dysfunction at 9 weeks of age, which is associated with impaired bioenergetics but not with mitochondrial ROS production.Graphical abstractGlobal ablation of the Uqcrh gene results in functional impairment of CIII associated with metabolic dysfunction and postnatal developmental arrest immediately after weaning from the mother. Uqcrh-KO mice show dramatically elevated blood glucose levels and decreased ability of isolated cardiac mitochondria to consume oxygen (O2). Impaired development (failure to thrive) after weaning manifests as a deficiency in the gain of body mass and growth of internal organ including the heart. The relative heart mass seemingly increases when organ mass calculated from transthoracic echocardiography (TTE) is normalized to body mass. Notably, the heart shows no signs of collagen deposition, yet does develop a contractile dysfunction reflected by a decrease in ejection fraction and fractional shortening.

Autopsy Findings and Inflammatory Markers in SARS-CoV-2: A Single-Center Experience.

The systemic inflammatory response related to COVID-19 can be easily investigated in living patients. Unfortunately, not every biomarker is suitable for postmortem analysis since several factors may interfere. The aim of this study was to summarize key histopathological findings within each organ system due to COVID-19 and to assess if serological inexpensive and widely available biomarkers such as CRP, IL-6, fibrinogen and d-Dimers, associated with adverse outcomes in COVID-19, can be implemented in a post-mortem assessment. A total of 60 subjects divided in 2 groups were included. All subjects died outside a hospital setting and therefore did not receive specific or symptomatic therapies that could have modulated the inflammatory response. The first group included 45 subjects in which mandatory autopsy was performed in order to establish the cause of death and macroscopic examination of the lungs was highly suggestive of SARS-CoV-2 infection. As controls (Group 2), 20 subjects who died from polytrauma in high velocity car accidents and suicide were selected. Bronchial fluids collected during the autopsy procedure were used for the RT-PCR diagnosis of SARS-CoV-2 and serum samples were sent for analysis of IL-6, CRP, d-Dimers and fibrinogen. Compared with the control group, the subjects of the COVID-19 group were older (59±19.5 vs.38±19.15 years, p=0.0002) and had more underlying comorbidities such as hypertension (60% vs 35%, p=0.06) or were overweight (53.3% vs 30%, p=0.08). The levels of CRP, IL-6, fibrinogen and d-Dimers in postmortem plasma samples were significantly higher in COVID-19 subjects than in control group (p< 0.0001). Moreover, the level of IL-6 was significantly higher in overweight patients (r=0.52, P<0.001). In all COVID-19 subjects, the histological examination revealed features corresponding to the exudative and/or proliferative phases of diffuse alveolar damage. Large pulmonary emboli were observed in 7 cases. Gross cardiac enlargement with left ventricular hypertrophy was observed in 19 cases. The most frequent pathological finding of the central nervous system was acute/early-subacute infarction. Due to the complexity of the inflammatory response, we postulate that a combination of biomarkers, rather than a single laboratory parameter, might be more effective in obtaining a reliable postmortem COVID-19 diagnosis.

Permanent Effect of SARS-CoV-2 on the Heart, Post Recovery

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Since December 2019, when the initial outbreak of COVID-19 occurred in China, a series of effective preventive control and medical treatment measures have been implemented, and have brought the pandemic under control to a certain extent. Most people infected with the virus will experience mild to moderate respiratory illness and recover without requiring special treatment. However, some will become seriously ill and require medical attention. A growing number of studies suggest many COVID-19 survivors experience some type of heart damage, even if they didn't have underlying heart disease and weren't sick enough to be hospitalized. Recent statistics estimate there being around 523.2 million cases of cardiovascular disease in the world, which represents the large population that this side effect or aftereffect potentially encompasses. According to research, there are structural changes in that take place when COVID enters a person’s body. In this case, the effect on the heart is relatively unknown or unproven. However, scientists and doctors have reported a couple of observations. First, the weight of the heart increased slightly after patients recovered from COVID. Second, Signs of cardiac enlargement and right ventricular dilatation were also noted. Under microscopic attention, scattered individual cardiomyocyte necrosis was visible as well. This paper will outline specific effects of COVID on the heart.

Diffuse myocardial fibrosis occurs in young patients with sickle cell anemia despite early disease-modifying therapy

Letter to Blood| March 16, 2023 Diffuse myocardial fibrosis occurs in young patients with sickle cell anemia despite early disease-modifying therapy Clinical Trials & Observations Cara E. Morin, Cara E. Morin ∗ 1Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH2Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN https://orcid.org/0000-0003-1953-4486 Search for other works by this author on: This Site PubMed Google Scholar Akshay Sharma, Akshay Sharma ∗ 3Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN https://orcid.org/0000-0003-3281-2081 Search for other works by this author on: This Site PubMed Google Scholar Subodh Selukar, Subodh Selukar 4Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN https://orcid.org/0000-0002-3802-488X Search for other works by this author on: This Site PubMed Google Scholar Gary Beasley, Gary Beasley 5Division of Pediatric Cardiology, University of Tennessee Health Science Center, Le Bonheur Children’s Hospital, Memphis, TN https://orcid.org/0000-0001-6137-6114 Search for other works by this author on: This Site PubMed Google Scholar Anthony Merlocco, Anthony Merlocco 2Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN5Division of Pediatric Cardiology, University of Tennessee Health Science Center, Le Bonheur Children’s Hospital, Memphis, TN6Division of Pediatric Radiology, University of Tennessee Health Science Center, Le Bonheur Children’s Hospital, Memphis, TN https://orcid.org/0000-0001-6228-0229 Search for other works by this author on: This Site PubMed Google Scholar Chris Goode, Chris Goode 2Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Parul Rai, Parul Rai 7Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN https://orcid.org/0000-0002-5770-7280 Search for other works by this author on: This Site PubMed Google Scholar Jeffrey A. Towbin, Jeffrey A. Towbin 5Division of Pediatric Cardiology, University of Tennessee Health Science Center, Le Bonheur Children’s Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Jane S. Hankins, Jane S. Hankins † 7Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN https://orcid.org/0000-0003-4439-7321 Search for other works by this author on: This Site PubMed Google Scholar Jason N. Johnson Jason N. Johnson † 2Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN5Division of Pediatric Cardiology, University of Tennessee Health Science Center, Le Bonheur Children’s Hospital, Memphis, TN6Division of Pediatric Radiology, University of Tennessee Health Science Center, Le Bonheur Children’s Hospital, Memphis, TN https://orcid.org/0000-0003-0712-1123 Search for other works by this author on: This Site PubMed Google Scholar Blood (2023) 141 (11): 1358–1362. https://doi.org/10.1182/blood.2022018209 Article history Submitted: August 26, 2022 Accepted: November 14, 2022 Connected Content This is a related article to: Heart failure in SCA: still challenging Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Cara E. Morin, Akshay Sharma, Subodh Selukar, Gary Beasley, Anthony Merlocco, Chris Goode, Parul Rai, Jeffrey A. Towbin, Jane S. Hankins, Jason N. Johnson; Diffuse myocardial fibrosis occurs in young patients with sickle cell anemia despite early disease-modifying therapy. Blood 2023; 141 (11): 1358–1362. doi: https://doi.org/10.1182/blood.2022018209 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Clinical Trials and Observations, Pediatric Hematology, Red Cells, Iron, and Erythropoiesis, Sickle Cell Disease, Transplantation TO THE EDITOR: We read with great interest the recent report from Niss et al.1 Our group has recently reviewed data from a similar population at our institution, which does not support the conclusion of Niss et al that diffuse myocardial fibrosis is prevented by early initiation of disease-modifying therapy (DMT). Cardiovascular complications are the leading cause of early mortality in patients with sickle cell anemia (SCA).2 Yet, the pathobiology of sickle cell cardiomyopathy is incompletely understood and likely multifactorial.3 Chronic anemia leads to global cardiac enlargement and myocardial hypertrophy. Global cardiac chamber dilation is a common feature in patients with SCA, and enlarged left atrial (LA) volume is a marker of diastolic dysfunction in SCA.4 Repetitive microvascular ischemic insults and associated reperfusion injury may contribute to diffuse myocardial fibrosis and myocardial remodeling in individuals with SCA....

Calsyntenin-1 Promotes Doxorubicin-induced Dilated Cardiomyopathy in Rats

PurposeDoxorubicin is an important cancer chemotherapeutic agent with severe cardiotoxic effects that eventually lead to dilated cardiomyopathy (DCM). Calsyntenin-1(CLSTN1) plays a critical role in the nervous system, but its relevance in cardiovascular diseases is unknown. We investigated the significance of CLSTN1 in doxorubicin-induced DCM.MethodsCLSTN1 expression in doxorubicin-induced DCM rats and H9c2 cells was determined using western blotting. To further explore the functions of CLSTN1, a cardiac-specific CLSTN1 overexpression rat model was constructed. The rats were subjected to analysis using echocardiographic, hemodynamic, and electrocardiographic parameters. Potential downstream molecules in CLSTN1 overexpression heart tissue were investigated using proteomics and western blotting. Finally, a knockdown of CLSTN1 was constructed to investigate the rescue function on doxorubicin-induced cell toxicity.ResultsCLSTN1 protein expression increased drastically in doxorubicin-induced DCM rats and H9c2 cells. Under doxorubicin treatment, CLSTN1 protein-specific overexpression in the heart muscle promoted cardiac chamber enlargement and heart failure, while the knockdown of CLSTN1 reduced doxorubicin-induced cardiomyocyte toxicity in vitro. At the mechanistic level, overexpression of CLSTN1 downregulated SERCA2 expression and increased the phosphorylation levels of PI3K-Akt and CaMK2.ConclusionOur findings demonstrated that CLSTN1 promotes the pathogenesis of doxorubicin-induced DCM. CLSTN1 could be a therapeutic target to prevent the development of doxorubicin-induced DCM.

Radiographic features of cardiogenic pulmonary oedema in cats with left-sided cardiac disease: 71 cases.

The aims of this study were to describe the radiographic features of cardiogenic pulmonary oedema (CPE) in a large group of cats with left-sided cardiac disease, and to determine the association between the radiographic features of CPE and the underlying cardiac disease. Thoracic radiographs of cats with CPE and echocardiographic evidence of left-sided cardiac disease and left atrial enlargement (LAE) were reviewed, and cardiac silhouette, pulmonary vessels and pulmonary parenchyma evaluation were performed. Interstitial and/or alveolar patterns were classified according to their distribution (ie, diffuse, multifocal or focal) and location (ie, craniodorsal, cranioventral, caudodorsal, caudoventral and perihilar). A Student's t-test and Mann-Whitney U-test, or the two-proportion z-test, were used to compare continuous or categorical variables, respectively, between cats affected by the two most represented cardiac diseases, namely hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM). Seventy-one cats were included; among them, 46 (64.7%) and 13 (18.3%) had presented for HCM and RCM, respectively. Subjective and objective cardiomegaly, and subjective and objective LAE were detected in 97.2% and 91.9% of cats and in 80.3% and 40.6% of cats, respectively. Pulmonary artery abnormalities, in particular caudal pulmonary artery dilation, were found in 77.5% of cats. Pulmonary artery to pulmonary vein ratio = 1 was found in 71.8% and 55% cats on right lateral and ventrodorsal or dorsoventral views, respectively. Interstitial (57.8%) and mixed interstitial-alveolar (38%) pattern, multifocal (84.5%) and symmetrical (75%) distribution with prevalent ventrocaudal (65.6% of cats) and ventrocranial (60.9% of cats) locations were most frequently observed. No difference was found for any of these radiographic features between cats with HCM and RCM. Moderate-to-severe cardiomegaly and LAE, caudal pulmonary artery and vein dilation, as well as a ventral, multifocal and symmetrical interstitial pulmonary pattern, were the main radiographic features of CPE in evaluated cats. Underlying cardiac disease did not influence the aforementioned radiographic features.