scholarly journals Late Cardiac Pathology in Severe Covid-19. A Postmortem Series of 30 Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Ana Ferrer-Gómez ◽  
Héctor Pian-Arias ◽  
Irene Carretero-Barrio ◽  
Antonia Navarro-Cantero ◽  
David Pestaña ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Immunohistochemical Analysis ◽  
Left Ventricular ◽  
Additional Patient ◽  
Tissue Samples ◽  
Disease Evolution ◽  
Cardiac Pathology ◽  
Coronary Artery Atherosclerosis ◽  
Cardiac Lesions ◽  
Prolonged Hospital

The role of SARS-CoV-2 as a direct cause in the cardiac lesions in patients with severe COVID-19 remains to be established. Our objective is to report the pathological findings in cardiac samples of 30 patients who died after a prolonged hospital stay due to Sars-Cov-2 infection. We performed macroscopic, histological and immunohistochemical analysis of the hearts of 30 patients; and detected Sars-Cov-2 RNA by RT-PCR in the cardiac tissue samples. The median age of our cohort was 69.5 years and 76.6% were male. The median time between symptoms onset and death was 36.5 days. The main comorbidities were arterial hypertension (13 patients, 43.3%), dyslipidemia (11 patients, 36.7%), cardiovascular conditions (8 patients, 26.7%), and obesity (8 patients, 26.7%). Cardiovascular conditions included ischemic cardiopathy in 4 patients (13.3%), hypertrophic cardiomyopathy in 2 patients (6.7%) and valve replacement and chronic heart failure in one patient each (3.3%). At autopsy, the most frequent histopathological findings were coronary artery atherosclerosis (8 patients, 26.7%), left ventricular hypertrophy (4 patients, 13.3%), chronic epicardial inflammation (3 patients, 10%) and adipose metaplasia (2 patients, 6.7%). Two patients showed focal myocarditis, one due to invasive aspergillosis. One additional patient showed senile amyloidosis. Sars-Cov-2 RNA was detected in the heart of only one out of 30 patients, who had the shortest disease evolution of the series (9 days). However, no relevant cardiac histological alterations were identified. In present series, cardiac pathology was only modest in most patients with severe COVID-19. At present, the contribution of a direct effect of SARS-CoV-2 on cardiac lesions remains to be established.

Abstract MP216: Identification Of Novel Phosphoprotein Signaling Pathways In Human Dilated Cardiomyopathy By Integrative Proteomic And Phosphoproteomic Analysis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Cristine J Reitz ◽  
Marjan Tavassoli ◽  
Da Hye Kim ◽  
Sina Hadipour-Lakmehsari ◽  
Saumya Shah ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Cardiac Tissue ◽  
Regulatory Element ◽  
Critical Role ◽  
Left Ventricular ◽  
Confocal Imaging ◽  
Intercalated Disc ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
And Function

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure, yet the majority of the underlying signaling mechanisms remain poorly characterized. Protein phosphorylation is a key regulatory element with profound effects on the activity and function of signaling networks; however, there is a lack of comprehensive phosphoproteomic studies in human DCM patients. We assessed the hypothesis that an integrative phosphoproteomics analysis of human DCM would reveal novel phosphoprotein candidates involved in disease pathophysiology. Combined proteomic and phosphoproteomic analysis of explanted left ventricular tissue samples from DCM patients ( n =4) and non-failing controls ( n =4) identified 5,570 unique proteins with 13,624 corresponding phosphorylation sites. From these analyses, we identified αT-catenin as a unique candidate protein with a cluster of 4 significantly hyperphosphorylated sites in DCM hearts ( P <0.0001), with no change in total αT-catenin expression at the protein level. Bioinformatics analyses of human datasets and confocal imaging of human and mouse cardiac tissue show highly cardiac-enriched expression of αT-catenin, localized to the cardiomyocyte intercalated disc. High resolution 3-dimensional reconstruction shows elongated intercalated disc morphology in DCM hearts (10.07±0.76 μm in controls vs. 17.20±1.87 μm in DCM, P <0.05, n =3/group), with significantly increased colocalization of αT-catenin with the intercalated disc membrane protein N-cadherin (Pearson’s coefficient 0.55±0.04 in controls vs. 0.71±0.02 in DCM, P <0.05, n =3/group). To investigate the functional role of cardiac αT-catenin phosphorylation, we overexpressed WT protein vs. non-phosphorylatable forms based on the loci identified in DCM hearts, in adult mouse cardiomyocytes using lentiviral transduction. Confocal imaging revealed significant internalization of the phospho-null form, as compared to the prominent intercalated disc staining of the WT protein (17.78±0.79% of WT vs. 9.25±0.49% of 4A mutant, P <0.0001, n =50 cells/group). Together, these findings suggest a critical role for αT-catenin phosphorylation in maintaining cardiac intercalated disc organization in human DCM.

Multiple left-sided cardiac lesions in one of Noonan's original patients

1999 ◽  
Vol 9 (6) ◽  
pp. 610-612 ◽  
Author(s):  
Jeffrey S. Danetz ◽  
Mary T. Donofrio ◽  
Richard P. Embrey
Keyword(s):  
Noonan Syndrome ◽  
Left Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Complex Case ◽  
Review Of The Literature ◽  
Cardiac Pathology ◽  
Left Ventricular Outflow ◽  
Cardiac Lesions ◽  
Pathology Review

AbstractWe describe a complex case of obstruction of the left ventricular outflow tract in one of Dr. Noonan's original patients. Intraoperative findings revealed pathology at the valvar, subvalvar and supravalvar positions. Patients with Noonan syndrome are traditionally described as having right-sided cardiac pathology. Review of the literature revealed left-sided lesions to occur in a substantial number of these patients. We therefore suggest the routine employment of cardiac ultrasonography in all patients with Noonan syndrome with attention directed toward left-sided pathology, as well as the frequent pulmonary valvar pathology.

scholarly journals Ajwa Nanopreparation Prevents Doxorubicin-Associated Cardiac Dysfunction: Effect on Cardiac Ischemia and Antioxidant Capacity

2019 ◽  
Vol 18 ◽  
pp. 153473541986235
Author(s):  
Soad Al-Jaouni ◽  
Seham Abdul-Hady ◽  
Hany El-Bassossy ◽  
Numan Salah ◽  
Magda Hagras
Keyword(s):  
Antioxidant Capacity ◽  
Cardiac Tissue ◽  
Reduced Glutathione ◽  
Cardiac Contractility ◽  
Left Ventricular Pressure ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Cardiac Ischemia ◽  
Tissue Samples ◽  
Before And After

Background: This study evaluated the cardioprotective effect of Ajwa nano-preparation against doxorubicin-associated cardiotoxicity. Methods: Twenty-four male Wistar rats (200-250 g) were divided into 3 groups. One group was given the nanopreparation containing both Ajwa fruit and pit in a dose of 1.4 g/kg orally 1 hour before doxorubicin infusion (Dates-DOX group). Another group was given the vehicle for 1 hour before doxorubicin infusion (DOX group). The third group received the vehicle but no DOX infusion (time control). Cardiac hemodynamics, blood pressure, cardiac contractility, and conductivity were recorded before and after 45 minutes of infusion of doxorubicin (15 mg/kg, slow intravenous over 45 minutes). Blood samples were collected before and after doxorubicin infusion. Heart tissue samples were collected and snap frozen until assay of reduced glutathione. Results: Rats pre-administered Ajwa nanopreparation were protected from doxorubicin-associated systolic and diastolic dysfunction based on the significant elevation in the rate of rise in left ventricular pressure (d p/d tmax) and (d p/d tmin) compared with the DOX group. In addition, it prevented the doxorubicin-associated ischemia based on the significant shortening in QT interval, JT interval, and Tpeak- Tend interval versus the DOX group. There was no effect on atrial conductivity (PR interval and P duration). Ajwa pretreatment increased the antioxidant capacity of cardiac tissue, as evidenced by increasing the cardiac content of reduced glutathione compared with the untreated doxorubicin group. Conclusion: Ajwa nanopreparation protects from doxorubicin-associated cardiotoxicity through alleviating cardiac ischemia and increasing cardiac antioxidant capacity.

Blood flow and high-energy phosphates in microregions of left ventricular subendocardium

1981 ◽  
Vol 240 (5) ◽  
pp. H804-H810 ◽  
Author(s):  
H. D. Kleinert ◽  
H. R. Weiss
Keyword(s):  
Blood Flow ◽  
Linear Relationship ◽  
Tissue Perfusion ◽  
High Energy ◽  
Left Ventricular ◽  
Significant Loss ◽  
Tissue Blood Flow ◽  
High Energy Phosphates ◽  
Tissue Samples ◽  
Heterogeneous Distribution

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

Myofibrillar degeneration with diphtheria toxin

2020 ◽  
Vol 45 (4) ◽  
pp. 351-357
Author(s):  
Bilge Özerman Edis ◽  
Muhammet Bektaş ◽  
Rüstem Nurten
Keyword(s):  
Protein Synthesis ◽  
Actin Filaments ◽  
Diphtheria Toxin ◽  
Cardiac Tissue ◽  
Culture Conditions ◽  
Bacterial Toxin ◽  
Filamentous Actin ◽  
Cardiac Damage ◽  
Tissue Samples

AbstractObjectivesCardiac damage in patient with diphtheritic myocarditis is reported as the leading cause of mortality. Diphtheria toxin (DTx) is a well-known bacterial toxin inducing various cytotoxic effects. Mainly, catalytic fragment inhibits protein synthesis, induces cytotoxicity, and depolymerizes actin filaments. In this study, we aimed to demonstrate the extent of myofibrillar damage under DTx treatment to porcine cardiac tissue samples.MethodsTissue samples were incubated with DTx for 1–3 h in culture conditions. To analyze whole toxin (both fragments) distribution, conjugation of DTx with FITC was performed. Measurements were carried out with fluorescence spectrophotometer before and after dialysis. Immunofluorescence microscopy was used to show localization of DTx-FITC (15 nM) on cardiac tissue incubated for 2 h. Ultrastructural characterization of cardiac tissue samples treated with DTx (15 or 150 nM) was performed with transmission electron microscopy.ResultsDTx exerts myofibrillar disorganization. Myofilament degeneration, mitochondrial damage, vacuolization, and abundant lipid droplets were determined with 150 nM of DTx treatment.ConclusionsThis finding is an addition to depolymerization of actin filaments as a result of the DTx-actin interactions in in vitro conditions, indicating that myofilament damage can occur with DTx directly besides protein synthesis inhibition. Ultrastructural results support the importance of filamentous actin degeneration at diphtheritic myocarditis.

Abstract P219: Differences in Phosphoproteins in Rodent versus Human Hearts: Implications for Translational Studies of Hypertensive Heart Disease

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Robert S Danziger ◽  
Kumar Kotlo ◽  
Allen Samarel ◽  
Hua Chen ◽  
Jared Aldstadt
Keyword(s):  
Heart Disease ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Troponin T ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Current Evidence ◽  
Tissue Samples ◽  
Pixel Intensity ◽  
Translational Studies

Background: Rodent models are commonly used to study hypertensive heart disease. Several recent studies have probed the level of correlation between specific signaling pathways and proteins in human and rodents. Current evidence is overwhelming that protein phosphorylations play a key role in cardiac remodeling. Methods: Left ventricular tissue samples were obtained from human systolic failing (n=5) and control (n=5) hearts and 3 rat models of hypertensive heart failure (aortic banding, Dahl salt-sensitive, and spontaneously hypertensive rats (SHR)) and corresponding controls. Total proteins were extracted and and phosphoenrichment performed. Phosphoproteins were separated by 2D-DIGE with Cydye staining. Gel images were registered and rectified for composite analysis and statistical comparisons using pixel intensity. Phosphoproteins were identified by MALDI-TOF/TOF Mass Spectrometry. Results: The patterns of overall protein abundance from normal and failing hearts were not statistically different. However, when the composite of human hearts were compared with composite patterns of phosphoproteins in normal and failing rodent hearts, there were profound differences in the phosphoprotein patterns in 26% of pixels in registered images (P < 0.05). Targeted pair wise analyses showed differences (P < 0.05) between human and rodent hearts for troponin T, myosin light chain, peroxiredoxin, and haptoglobin phosphorylations. Conclusions: Together, the present results indicate significant differences in cardiac phosphoproteins in human versus rodent heart and the importance of confirming findings from rodent studies in humans for translational studies of kinases, phosphatases, and phosphoproteins. This may specifically relate to studies of phosphorylation of myosin light chain and troponin.

Cardiac Manifestations of Rocky Mountain Spotted Fever

PEDIATRICS ◽  
1981 ◽  
Vol 67 (3) ◽  
pp. 358-361
Author(s):  
José Marin-Garcia ◽  
W. M. Gooch ◽  
Daniel L. Coury
Keyword(s):  
Spotted Fever ◽  
Rocky Mountain ◽  
Myocardial Necrosis ◽  
The United States ◽  
Left Ventricular ◽  
Chest Roentgenogram ◽  
Rocky Mountain Spotted Fever ◽  
Close Observation ◽  
Cardiac Lesions ◽  
Cardiac Manifestations

An increasing incidence of Rocky Mountain spotted fever is being noted across the United States. From 1955 to 1978 80 children with this disease were seen in a children's hospital. Autopsies were performed in six of the nine fatal cases, and cardiac lesions were seen in each. Multifocal myocarditis with petechiae was present in four cases, and in two of them there were areas of myocardial necrosis. In four of the necropsied cases there were electrocardiographic changes and cardiac enlargement on chest roentgenogram. Among survivors five patients manifested at least one cardiac abnormality. ST-T changes were noted in two patients, atrioventricular conduction disturbance in two, and severe left ventricular hypertrophy in one patient. Cardiomegaly was observed in three patients, and one had severe cardiac failure that responded to medical management. Cardiac involvement is frequently present in Rocky Mountain spotted fever, and close observation seems to be warranted.

Abstract P195: No Functional Nerve Recovery To 6 Months Post Renal Denervation With Rf Energy In A Normotensive Pig Model

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Andrew Sharp ◽  
Stefan Tunev ◽  
Markus P Schlaich ◽  
David P LEE ◽  
Aloke Finn ◽  
...  
Keyword(s):  
Animal Studies ◽  
Renal Denervation ◽  
Blood Pressure Reduction ◽  
Immunohistochemical Analysis ◽  
Swine Model ◽  
Renal Nerve ◽  
Tissue Samples ◽  
Axon Density ◽  
Rf Energy

Background: The safety and efficacy of catheter-based radio frequency (RF) renal denervation (RDN) have been demonstrated in randomized, sham-controlled trials. Long-term durability of blood pressure reduction following RDN has also been demonstrated by all-comer registries, although published pre-clinical reports of functional renal nerve regrowth are not consistent. We quantified the processes that support RDN procedural durability utilizing animal models. Methods: Animal studies were conducted in accordance with published guidelines. RDN was performed (4 lesions in the main renal artery) in normotensive swine using the Symplicity Spyral™ RDN system (Medtronic, Santa Rosa, CA, USA). Two additional groups not undergoing RDN served as control. Serial histological tissue samples were obtained in separate groups at 7 (n=12/group) and 180 (N=16/group) days post-procedure in all animals followed by bioanalytical quantification of cortical norepinephrine (NE) levels and immunohistochemical analysis of renal cortical axon density in matched samples. Results: Renal cortical axon density and NE levels were significantly reduced at 7 days and persisted through 180 days following RDN compared with control ( Figure ). Nerve fibrosis and necrosis were observed in the region of ablation, while nerve body atrophy was apparent distal to ablation location at 180 days. Conclusions: Reductions in both NE and renal cortical axon density were sustained at 7 and 180 days post-RDN procedure using RF renal denervation in a normotensive swine model. These data confirm and extend other pre-clinical and clinical evidence of long-term durability of the RDN procedure using RF energy.

Abstract 15607: Right Atrial Reservoir Strain Predicts Survival in Patients With Cardiac Amyloidosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Peter Huntjens ◽  
Kathleen Zhang ◽  
Yuko Soyama ◽  
Maria Karmpalioti ◽  
Daniel Lenihan ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Ventricular Hypertrophy ◽  
Cardiac Tissue ◽  
Fold Increase ◽  
Left Ventricular ◽  
Right Atrial ◽  
Chamber View ◽  
All Cause Mortality ◽  
And Function

Introduction: Myofibril deposition in amyloidosis diffusely may affect cardiac structure and function. Right ventricular involvement has been associated with adverse clinical outcome. However, the utility of right atrial (RA) function assessment by echocardiographic strain imaging is unclear. Hypothesis: We hypothesize that right atrial stain has prognostic value in cardiac amyloidosis. Methods: We studied 121 consecutive patients with cardiac amyloidosis: 18% had transthyretin and 79% had light chain amyloidosis. Cardiac amyloidosis was either confirmed by endocardial biopsy (36%) or by a combination of non-cardiac tissue biopsy and proof of left ventricular hypertrophy (64%). Speckle tracking peak RA reservoir strain was assessed based on 6 segments from the apical 4-chamber view. All-cause mortality was tracked over a median of 5 years. Results: Echocardiographic peak longitudinal RA strain was feasible in 109 patients (90%). 60 CA patients died during follow-up period. Peak longitudinal RA strain was reduced in cardiac amyloidosis non-survivors (8.1%) in comparison to survivors (18.3%, p<0.01), showing RA involvement in cardiac amyloidosis. Peak RA strain was significantly associated with survival (using median 12.5%) (p<0.001). Low peak longitudinal RA strain was associated with a 3.3-fold increase in mortality risk (95% confidence interval: 1.83 - 5.96). Conclusions: Reduced peak longitudinal RA strain was significantly associated with survival in patients with cardiac amyloidosis. RA reservoir function assessed by strain appears to be useful as a new means to predict prognosis in cardiac amyloidosis patients and has promise for clinical application.

Sign in / Sign up

Export Citation Format

Share Document