SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo.

BACKGROUND: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. METHODS: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. RESULTS: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. CONCLUSIONS: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

Contemporary Role of Positron Emission Tomography (PET) in Endocarditis: A Narrative Review.

Endocarditis, a serious infectious disease, remains a diagnostic challenge in contemporary clinical practice. The advent of advanced imaging modalities has contributed significantly to the improved understanding and management of this complex disease. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging has shown remarkable potential in improving the diagnostic accuracy of endocarditis. In the update of the Modified Duke Criteria, in 2023, The International Society for Cardiovascular Infectious Diseases (ISCVID) Working Group recognized specific 18F-FDG PET/CT findings as a major diagnostic criterion, particularly in patient with prosthetic valve endocarditis. The ability of PET to visualize metabolic activity allows for the identification of infective foci and could differentiate between infective and non-infective processes. This review examines the clinical utility of PET in differentiating infective endocarditis from other cardiovascular pathologies, highlighting its sensitivity and specificity in detecting native and prosthetic valve infections, including patients with transcatheter aortic valve implantation (TAVI), cardiac implantable devices (CIEDs), and left ventricular assistance devices (LVAD). Also, practical aspects and indications are illustrated to optimize the quality of imaging and reduce potential false positive results. In conclusion, the current use of PET in endocarditis has become a valuable diagnostic tool; as technological advances continue, PET will play an increasingly important role in the multidisciplinary approach to the management of endocarditis.

Coronary artery mycotic aneurysm in a patient suffering from subacute endocarditis: a case report and literature review.

Although mycotic aneurysm is a known and important disease in the cerebrovascular system, especially the brain, there are scarce reports about coronary artery mycotic aneurysms (CAMA). CAMA can occur not only in the context of endocarditis but also as a rare adverse event of coronary artery stenting, which has been used more extensively in recent years. Accordingly, it is essential to pay greater attention to its associated presentations and clinical course. Considering the scant evidence available, reporting the disease course of each patient with CAMA can help increase the physician's knowledge about this condition, which is why we are reporting this case. A 42-year-old man with diabetes was referred to our center with embolic left cerebellar infarction 3 months earlier, as well as a 2-month history of feverishness before his referral. His blood culture was positive for Viridans Streptococci, and he had paraclinical signs of inflammation and two- and three-dimensional transthoracic and transesophageal echocardiography (2D & 3D TTE and TEE) signs of aortic and mitral valves' infective endocarditis with the destruction of the aortic valve, severe aortic and mitral regurgitation, severe pulmonary hypertension, and moderate biventricular systolic dysfunction. Regarding the obviously dilated left main coronary artery on TEE images, contrast-enhanced chest multidetector computed tomography was performed for better assessment of coronary arteries with suspicion of CAMA, which confirmed aneurysmal dilatation of the proximal left main coronary artery. The presence of bacteria was confirmed on staining the valvular tissue, resected during the surgical replacement of aortic and mitral valves. As the cardiac surgeon considered CAMA resection and coronary bypass grafting high risk for the patient, he received parenteral antibiotic therapy, for 6 weeks. At 1-year follow-up, he was doing well with no signs/symptoms of endocarditis and well-functioning mechanical prosthetic valves. This case shows the significance of considering CAMA in the setting of endocarditis, resistant to medical and/or surgical therapy or in patients with coronary aneurysm, simultaneous with active endocarditis. Therefore, more attention should be paid to this extravalvular complication of endocarditis, and its possibility should be considered and investigated in any patient presented with valvular endocarditis, especially involving the aortic valve.

Survey of Bacterial Isolates and Their Antimicrobial Susceptibility Patterns from Dogs with Infective Endocarditis.

Infective endocarditis (IE) is a potentially fatal disease in dogs. Limited information exists regarding the characterization of bacterial isolates from dogs with IE. The objective of this study was to describe bacterial isolates associated with IE and their antimicrobial susceptibility patterns. A retrospective analysis of dogs with IE and bacterial isolates was performed, and antimicrobial susceptibility was interpreted using current veterinary cut points where available. The susceptibility rate was assessed for association with survival and previous antimicrobial administration. Fifty-one bacterial isolates were identified from 45 dogs, and 33 had antimicrobial susceptibility performed. Staphylococcus spp. (14/51; 27.5%) was the most common organism. Antimicrobials with the lowest susceptibility rate were ampicillin (19/26; 73%), doxycycline (16/22; 73%), and enrofloxacin (22/29; 76%) with 12/33 (36%) of isolates exhibiting multidrug resistance (MDR). Individual antimicrobial resistances and the MDR rate were not associated with a difference in survival rate. Bacterial isolates from dogs that had received fluoroquinolone antimicrobials in the month before diagnosis had a higher rate of non-intrinsic fluoroquinolones resistance (5/8;62.5%) compared to those that did not receive fluoroquinolones (2/21; 9.5%) (p = 0.03). Antimicrobial resistance and MDR phenotype were common in this study. Culture and antimicrobial susceptibility testing should be pursued in dogs with IE to help guide antimicrobial therapy.

Outcome and prognostic factors in infective endocarditis in dogs: 113 cases (2005-2020).

BACKGROUND: Factors associated with outcome in dogs diagnosed with infective endocarditis (IE) are not well characterized. OBJECTIVES: Evaluate outcome and prognostic factors in dogs with IE. ANIMALS: One hundred and thirteen dogs with IE. METHODS: Medical records for dogs that fulfilled the modified Duke criteria between 2005 and 2020 were retrospectively reviewed. Signalment, preexisting conditions, clinicopathologic findings, treatment regimen, and outcomes were recorded. Univariate logistic regression was performed to identify categorical factors associated with mortality, and then multivariate analysis was performed. RESULTS: Dogs were categorized as survivors (n = 47), non-survivors (n = 57), or lost to follow-up (n = 9). Survival to discharge and at 1 month was documented in 79 (70%) of 113 and 56 (54%) of 104 dogs, respectively, with median survival time (MST) of 72 days. Risk factors associated with mortality included development of congestive heart failure (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.4-97.8), thromboembolic events (OR, 5.7; 95% CI, 2.3-14.4), and acute kidney injury (OR, 6.2; 95% CI, 2.0-18.8). Administration of antithrombotic medications was associated with survival (OR, 0.35; 95% CI, 0.13-0.97). Dogs that were not treated with antithrombotics had MST of 92 days, whereas dogs treated with antithrombotics did not reach MST during the study period. The heart valves involved and etiologic agent identified did not correlate with outcome. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with IE that had thromboembolic events, acute kidney injury, or congestive heart failure had higher risk of mortality. Administration of antithrombotics was associated with prolonged survival time.

Cardiac SARS-CoV-2 infection is associated with pro-inflammatory transcriptomic alterations within the heart.

AIMS: Cardiac involvement in COVID-19 is associated with adverse outcome. However, it is unclear whether cell-specific consequences are associated with cardiac SARS-CoV-2 infection. Therefore, we investigated heart tissue utilizing in situ hybridization, immunohistochemistry, and RNA-sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19. METHODS AND RESULTS: In this study, 95 SARS-CoV-2-positive autopsy cases were included. A relevant SARS-CoV-2 virus load in the cardiac tissue was detected in 41/95 deceased (43%). Massive analysis of cDNA ends (MACE)-RNA-sequencing was performed to identify molecular pathomechanisms caused by the infection of the heart. A signature matrix was generated based on the single-cell dataset 'Heart Cell Atlas' and used for digital cytometry on the MACE-RNA-sequencing data. Thus, immune cell fractions were estimated and revealed no difference in immune cell numbers in cases with and without cardiac infection. This result was confirmed by quantitative immunohistological diagnosis. MACE-RNA-sequencing revealed 19 differentially expressed genes (DEGs) with a q-value <0.05 (e.g. up: IFI44L, IFT3, TRIM25; down: NPPB, MB, MYPN). The upregulated DEGs were linked to interferon pathways and originate predominantly from endothelial cells. In contrast, the downregulated DEGs originate predominately from cardiomyocytes. Immunofluorescent staining showed viral protein in cells positive for the endothelial marker ICAM1 but rarely in cardiomyocytes. The Gene Ontology (GO) term analysis revealed that downregulated GO terms were linked to cardiomyocyte structure, whereas upregulated GO terms were linked to anti-virus immune response. CONCLUSION: This study reveals that cardiac infection induced transcriptomic alterations mainly linked to immune response and destruction of cardiomyocytes. While endothelial cells are primarily targeted by the virus, we suggest cardiomyocyte destruction by paracrine effects. Increased pro-inflammatory gene expression was detected in SARS-CoV-2-infected cardiac tissue but no increased SARS-CoV-2 associated immune cell infiltration was observed.

Identification of Streptococcus suis in a cat with endomyocarditis.

CASE SUMMARY: A 3-year-old neutered male domestic mediumhair cat was evaluated for a 4-month history of a fever that was responsive to pradofloxacin. A grade III/VI left parasternal systolic heart murmur was noted on examination. Findings on thoracic radiography were consistent with left-sided congestive heart failure and findings on echocardiographic examination suggested endomyocarditis. Aerobic blood cultures yielded growth of a Streptococcus species that was identified as Streptococcus suis using both matrix-associated laser desorption ionization-time of flight mass spectrometry and 16S rRNA gene sequencing. The cat was treated but clinically deteriorated and was euthanized 23 days after diagnosis. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of S suis bacteremia, an emerging pathogen, in association with endomyocarditis in the cat. This case also highlights the role of echocardiography to document progressive hemodynamic changes as a result of valvular erosion in the course of infective endocarditis treatment and the role of blood cultures as a diagnostic tool in cats presenting with fever.

SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function.

COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or are secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that that SARS-CoV-2 selectively infects hPSC-CMs through the viral receptor ACE2, whereas in hPSC-SMCs there is minimal viral entry or replication. After entry into cardiomyocytes, SARS-CoV-2 is assembled in lysosome-like vesicles and egresses via bulk exocytosis. The viral transcripts become a large fraction of cellular mRNA while host gene expression shifts from oxidative to glycolytic metabolism and upregulates chromatin modification and RNA splicing pathways. Most importantly, viral infection of hPSC-CMs progressively impairs both their electrophysiological and contractile function, and causes widespread cell death. These data support the hypothesis that COVID-19-related cardiac symptoms can result from a direct cardiotoxic effect of SARS-CoV-2.

Prevalence of Bartonella sp. in United States military working dogs with infectious endocarditis: a retrospective case-control study.

OBJECTIVES: Bartonella infection has been associated with endocarditis in humans, dogs, cats and cattle. In order to evaluate the importance of this pathogen as a possible source of endocarditis in United States military working dogs (MWDs), we performed a retrospective case-control study on 26 dogs with histological diagnosis of culture negative endocarditis (n = 18), endomyocarditis (n = 5) or endocardiosis (n = 3) and 28 control dogs without any histological cardiac lesions. METHODS: DNA was extracted from paraffin embedded cardiac valves and tissues from case and control dogs and submitted to PCR testing with primers targeting the Bartonella gltA gene. PCR-RFLP using four restriction endonucleases and partial sequencing was then performed to determine the Bartonella species involved. RESULTS: Nineteen (73%) cases were PCR positive for Bartonella, including B. henselae (8 dogs), B. vinsonii subsp. berkhoffii (6 dogs), B. washoensis (2 dogs) and B. elizabethae (1 dog). Only one control dog was weakly PCR positive for Bartonella. Based on the type of histological diagnosis, 13 (72.2%) dogs with endocarditis, 3 (60%) dogs with endomyocarditis and all 3 dogs with endocardiosis were Bartonella PCR positive. CONCLUSIONS: Bartonella sp. Infections were correlated with cardiopathies in US military working dogs. Systemic use of insecticides against ectoparasites and regular testing of MWDs for Bartonella infection seem highly appropriate to prevent such life-threatening exposures.

Acute primary purulent pericarditis in an adult patient with unknown X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is a rare form of inherited immunodeficiency due to an impairment in B-lymphocyte differentiation and maturation. In the majority of cases XLA is diagnosed in childhood, particularly among males affected by recurrent infections and with a family history of immunodeficiency. Infections of respiratory tract, gastrointestinal apparatus, eyes, nose and ears are frequent in XLA patients; on the contrary, infections of myocardium, cardiac valves and pericardium are rarely described in XLA. A 34-year-old man with unknown XLA was hospitalized because of syncope, due to pericardial tamponade, caused by acute primary purulent pericarditis. Immediate pericardiocentesis was effective in improving hemodynamics, and empiric antibiotic therapy was successful in controlling the infection. Purulent pericarditis is a rare disease with high mortality rate: it is usually caused by hematogenous bacterial propagation, direct infection of pericardial space by chest wounds or thoracic surgery, or extension of infection from adjacent tissues. However, this patient had no recent local or systemic infections. Because of unusual clinical picture during hospitalization he underwent further clinical and laboratory evaluations, that showed low immunoglobulin levels. After exclusion of acquired immunodeficiency, genetic tests were performed: they detected deletion of exons 8-9-10 of Bruton Tyrosine Kinase gene on X chromosome, leading to the diagnosis of XLA. Acute purulent primary pericarditis may also occur in adult XLA patients as first clinical manifestation. According to this case report, a primary immunodeficiency syndrome should be considered in patients with atypical cardiac infections and no predisposing conditions, regardless of age.

Acupuncture-Related Cardiac Complications: A Systematic Review.

BACKGROUND: The objective of this study is to review acupuncture-related cardiac complications, such as infective endocarditis (IE), cardiac tamponade (CT), pericarditis, and cardiac rupture, as there is no known reported literature to determine the burden of cardiac adverse events due to acupuncture. METHODS: Structured computerized databases were searched using the special Medical Subject Heading (MeSH). Manual search using the references of relevant articles was also performed. RESULTS: A total of 133 articles were initially retrieved, but careful reading resulted in only 30 cases of relevant cardiac adverse events. There were 8 articles of infective complications (mostly IE), while 22 articles of CT have been reported to date. The diagnoses were made with echocardiography and patients were treated with intravenous antibiotics. The source of the infection was mostly localized to acupuncture needle prick sites, such as earlobes and legs. Mortality rate for post-acupuncture CT was not significantly higher than infective cardiac complication (Pearson's Chi-square = 0.559; likelihood ratio = 0.553). However, the weighted percentage of death was about 80% in CT vs only 20% mortality for infective cardiac complications. On the other hand, CT was the most common presentation when the needle pricks were close to the heart, and had a clinical presentation of hypotension and venous distention. CONCLUSIONS: Although the universally reported complications of acupuncture are low, and the procedure itself has been deemed low risk in acupuncture-related literature, these cardiac complications are alarming. To avoid these potentially catastrophic consequences, more education needs to be done for adopting safer techniques.

Necrotizing infection of the heart.

A case of necrotizing infection of the heart is presented. A 70-year-old woman presented with vague chest and abdominal pain. CT of the abdomen and pelvis was initially obtained, which demonstrated gas in the myocardium of the left ventricle. Subsequent chest CT, endoscopy, and abdominal surgical exploration did not reveal perforated viscus or diaphragm compromise. At median sternotomy, the inferior wall of the heart was found to be necrotic. Culture of the excised tissue grew E. coli. The patient expired shortly after surgical exploration.

The Equine Neonatal Cardiovascular System in Health and Disease.

The neonatal foal is in a transitional state from prenatal to postnatal circulation. Healthy newborn foals often have cardiac murmurs and dysrhythmias, which are usually transient and of little clinical significance. The neonatal foal is prone to infection and cardiac trauma. Echocardiography is the main tool used for valuation of the cardiovascular system. With prompt identification and appropriate action, dysrhythmias and other sequel to cardiac trauma can be corrected. With infection, the management and prognosis are driven by concurrent sepsis. Congenital disease represents an interesting diagnostic challenge for the neonatologist, but surgical correction is not appropriate for most equids.

A life-threatening infective pseudoaneurysm of the left ventricle in a toddler.

Pseudoaneurysms of the ventricle are an uncommon occurrence in children. They may be secondary to previous cardiac surgery or infection of the pericardial space. Infective pseudoaneurysms require urgent surgery because rupture of the pseudoaneurysm may have catastrophic consequences. The outcome with surgery is excellent. We report a toddler with ruptured pseudoaneurysm secondary to purulent pericarditis who recovered with an emergency surgical closure of the opening of the pseudo-aneurysm.