Observation of Myocardial Involvement in Patients Recovered From COVID-19 by Using Cardiac Magnetic Resonance Imaging, In a Tertiary Care Hospital, Bangladesh.

It was previously reported that coronavirus caused myocardial injury in hospitalized patients. However, delayed cardiac involvement in symptomatic patient recovery from COVID-19 is not yet well known. The objective of this study was to evaluate cardiac involvement by using cardiac magnetic resonance (CMR) in symptomatic post-COVID-19 recovered patients. Thirty (30) patients who recovered from COVID-19 and had recently reported cardiac symptoms were studied in a prospective observational study performed at Popular Medical College Hospital, Dhaka, Bangladesh from March 2021 to September 2021. They underwent CMR examinations. CMR scanning protocol included the following: black blood, cine sequence, both short-axis and long-axis, T2-weight short tau inversion recovery (STIR) sequence, T2- weighted imaging (T2WI) and late gadolinium enhancement (LGE) and quantitative mapping sequences-native T1/T2 mapping and post-contrast T1 mapping. Myocardial edema and late gadolinium enhancement were assessed in all patients. Quantitative evaluation of native T1/T2 and ECV value and cardiac function were evaluated. There were 30 people in all in this study. The average age of the participants in the study was 36.6 years. Fourteen (46.6%) of the patients had abnormal cardiac MRI results, while the remaining 15(53.3%) had negative CMR findings. Among positive findings patients, 8(57.1%) of 14 had increased T2 signal. Increased myocardial edema was found in the same no of patients, involving 53.2% (128 of 224) of LV segments. Only 2 cases (2 of 14) showed mid myocardial and subepicardial LGE, involving 18 of 224, 8.03% of myocardial segments. Global native T1, T2 and ECV values are significantly elevated in all CMR positive findings patients. Native T1 1231ms (IQR: 1281.25-1257.5 versus 1155.5 (IQR: 1137.25-1172.75), T2 40 (IQR: 34.5-43.25) versus 35.5 (IQR: 34-37), ECV 31 (29.75-33.25) versus 23.5 (21.25-24.0), p<0.001; p<0.011 and p<0.001 respectively. Reduced RV functional were found in positive as compared with negative CMR findings patients, EF, 32.05 (IQR: 25.25-39.0) versus 54.5 (IQR: 52.0-57.75) and EDV, 117.5 (IQR: 102.0-134.25) versus 95.0 (IQR: 71.75-99.75), p<0.001 and p<0.001 respectively. In this study cardiac involvement was found in the post-COVID-19 recovered patient with cardiac symptoms. Cardiac MRI findings included myocardial edema, fibrosis and reduced right ventricular function. So attention should be paid to symptomatic post-COVID-19 recovered patients.

T2 mapping in myocardial disease: a comprehensive review.

Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for myocardial tissue characterization. Elevated transverse relaxation time (T2) is specific for increased myocardial water content, increased free water, and is used as an index of myocardial edema. The strengths of quantitative T2 mapping lie in the accurate characterization of myocardial edema, and the early detection of reversible myocardial disease without the use of contrast agents or ionizing radiation. Quantitative T2 mapping overcomes the limitations of T2-weighted imaging for reliable assessment of diffuse myocardial edema and can be used to diagnose, stage, and monitor myocardial injury. Strong evidence supports the clinical use of T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy. Accumulating data support the utility of T2 mapping for the assessment of other cardiomyopathies, rheumatologic conditions with cardiac involvement, and monitoring for cancer therapy-related cardiac injury. Importantly, elevated T2 relaxation time may be the first sign of myocardial injury in many diseases and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. This comprehensive review discusses the technical considerations and clinical roles of myocardial T2 mapping with an emphasis on expanding the impact of this unique, noninvasive tissue parameter.

The role of cardiovascular magnetic resonance in the evaluation of acute myocarditis and inflammatory cardiomyopathies in clinical practice - a comprehensive review.

Inflammatory cardiomyopathy (I-CMP) is defined as myocarditis in association with cardiac dysfunction and/or ventricular remodelling. It is characterized by inflammatory cell infiltration into the myocardium and has heterogeneous infectious and non-infectious aetiologies. A complex interplay of genetic, autoimmune, and environmental factors contributes to the substantial risk of deteriorating cardiac function, acute heart failure, and arrhythmia as well as chronic dilated cardiomyopathy and its sequelae. Multi-parametric cardiovascular magnetic resonance (CMR) imaging is sensitive to many tissue changes that occur during myocardial inflammation, regardless of its aetiology. In this review, we summarize the various aetiologies of I-CMP and illustrate how CMR contributes to non-invasive diagnosis.

Cardiomyopathy Associated with Anti-SARS-CoV-2 Vaccination: What Do We Know?

The SARS-CoV-2 pandemic has mobilized many efforts worldwide to curb its impact on morbidity and mortality. Vaccination of the general population has resulted in the administration of more than 6,700,000,000 doses by the end of October 2021, which is the most effective method to prevent hospitalization and death. Among the adverse effects described, myocarditis and pericarditis are low-frequency events (less than 10 per 100,000 people), mainly observed with messenger RNA vaccines. The mechanisms responsible for these effects have not been specified, considering an exacerbated and uncontrolled immune response and an autoimmune response against specific cardiomyocyte proteins. This greater immunogenicity and reactogenicity is clinically manifested in a differential manner in pediatric patients, adults, and the elderly, determining specific characteristics of its presentation for each age group. It generally develops as a condition of mild to moderate severity, whose symptoms and imaging findings are self-limited, resolving favorably in days to weeks and, exceptionally, reporting deaths associated with this complication. The short- and medium-term prognosis is favorable, highlighting the lack of data on long-term evolution, which should be determined in longer follow-ups.

COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury.

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

Immunomodulatory Role of Tenascin-C in Myocarditis and Inflammatory Cardiomyopathy.

Accumulating evidence suggests that the breakdown of immune tolerance plays an important role in the development of myocarditis triggered by cardiotropic microbial infections. Genetic deletion of immune checkpoint molecules that are crucial for maintaining self-tolerance causes spontaneous myocarditis in mice, and cancer treatment with immune checkpoint inhibitors can induce myocarditis in humans. These results suggest that the loss of immune tolerance results in myocarditis. The tissue microenvironment influences the local immune dysregulation in autoimmunity. Recently, tenascin-C (TN-C) has been found to play a role as a local regulator of inflammation through various molecular mechanisms. TN-C is a nonstructural extracellular matrix glycoprotein expressed in the heart during early embryonic development, as well as during tissue injury or active tissue remodeling, in a spatiotemporally restricted manner. In a mouse model of autoimmune myocarditis, TN-C was detectable before inflammatory cell infiltration and myocytolysis became histologically evident; it was strongly expressed during active inflammation and disappeared with healing. TN-C activates dendritic cells to generate pathogenic autoreactive T cells and forms an important link between innate and acquired immunity.

Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications.

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to the rapidly increased prevalence of overweight and obesity. To this point, epidemiological, clinical, and experimental evidence supports the existence of a unique disease entity termed "obesity cardiomyopathy," which develops independent of hypertension, coronary heart disease, and other heart diseases. Our contemporary review evaluates the evidence for this pathological condition, examines putative responsible mechanisms, and discusses therapeutic options for this disorder. Clinical findings have consolidated the presence of left ventricular dysfunction in obesity. Experimental investigations have uncovered pathophysiological changes in myocardial structure and function in genetically predisposed and diet-induced obesity. Indeed, contemporary evidence consolidates a wide array of cellular and molecular mechanisms underlying the etiology of obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover of free fatty acids, lipotoxicity, and amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, myocardial fibrosis, dampened coronary flow reserve, coronary microvascular disease (microangiopathy), and endothelial impairment. Given the important role of obesity in the increased risk of heart failure, especially that with preserved systolic function and the recent rises in COVID-19-associated cardiovascular mortality, this review should provide compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions, underlying mechanisms, and offer new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy.

Molecular pathways triggered by COVID-19 in different organs: ACE2 receptor-expressing cells under attack? A review.

OBJECTIVE: In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease. MATERIALS AND METHODS: PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. RESULTS: The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed. CONCLUSIONS: The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.

Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study.

AIMS: Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction. The cardiac pathological changes in these patients with COVID-19 have yet to be well described. METHODS AND RESULTS: In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists. The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry. Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement. Lymphocytic myocarditis was present in 3 (14%) of the cases. In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant. Increased interstitial macrophage infiltration was present in 18 (86%) of the cases. A mild pericarditis was present in four cases. Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases. There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified. CONCLUSIONS: In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases. Other forms of myocardial injury are also present in these patients. The macrophage infiltration may reflect underlying diseases rather than COVID-19.

[Cardiac biomarkers and COVID-19 - Phenotypes and Interpretation]. / Kardiale Biomarker und COVID-19-Phänotypen und Interpretation.

Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.