Interaction of COVID-19 With Common Cardiovascular Disorders.

The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.

Vitamin C Regulates the Profibrotic Activity of Fibroblasts in In Vitro Replica Settings of Myocardial Infarction.

Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 µg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.

Cardiac magnetic resonance T2* mapping in patients with COVID-19 pneumonia is associated with serum ferritin level?

The coronavirus disease of 2019 (COVID-19)-related myocardial injury is an increasingly recognized complication and cardiac magnetic resonance imaging (MRI) has become the most commonly used non-invasive imaging technique for myocardial involvement. This study aims to assess myocardial structure by T2*-mapping which is a non-invasive gold-standard imaging tool for the assessment of cardiac iron deposition in patients with COVID-19 pneumonia without significant cardiac symptoms. Twenty-five patients with COVID-19 pneumonia and 20 healthy subjects were prospectively enrolled.Cardiac volume and function parameters, myocardial native-T1, and T2*-mapping were measured. The association of serum ferritin level and myocardial mapping was analyzed. There was no difference in terms of cardiac volume and function parameters. The T2*-mapping values were lower in patients with COVID-19 compared to controls (35.37 [IQR 31.67-41.20] ms vs. 43.98 [IQR 41.97-46.88] ms; p < 0.0001), while no significant difference was found in terms of native-T1 mapping value(p = 0.701). There was a positive correlation with T2*mapping and native-T1 mapping values (r = 0.522, p = 0.007) and negative correlation with serum ferritin values (r = - 0.653, p = 0.000), while no correlation between cardiac native-T1 mapping and serum ferritin level. Negative correlation between serum ferritin level and T2*-mapping values in COVID-19 patients may provide a non-contrast-enhanced alternative to assess tissue structural changes in patients with COVID-19. T2*-mapping may provide a non-contrast-enhanced alternative to assess tissue alterations in patients with COVID-19. Adding T2*-mapping cardiac MRI in patients with myocardial pathologies would improve the revealing of underlying mechanisms. Further in vivo and ex vivo animal or human studies designed with larger patient cohorts should be planned.

SARS-CoV-2-Induced Myocarditis: A State-of-the-Art Review.

In this review, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly cause myocarditis with severe myocardial damage induced by viral particles. A review of the major data published from 2020 to 2022 was performed by consulting the major databases alongside first-hand experiences that emerged from the cardiac biopsies and autopsy examinations of patients who died of SARS-CoV-2 infections. From this study, a significantly large amount of data suggests that the Dallas criteria were met in a residual percentage of patients, demonstrating that SARS-CoV-2 myocarditis was a rare clinical and pathological entity that occurred in a small percentage of subjects. All cases described here were highly selected and subjected to autopsies or endomyocardial biopsies (EMBs). The most important discovery, through the detection of the SARS-CoV-2 genome using the polymerase chain reaction, consisted in the presence of the viral genome in the lung tissue of most of the patients who died from COVID-19. However, the discovery of the SARS-CoV-2 viral genome was a rare event in cardiac tissue from autopsy findings of patients who died of myocarditis It is important to emphasize that myocardial inflammation alone, as promoted by macrophages and T cell infiltrations, can be observed in noninfectious deaths and COVID-19 cases, but the extent of each cause is varied, and in neither case have such findings been reported to support clinically relevant myocarditis. Therefore, in the different infected vs. non-infected samples examined, none of our findings provide a definitive histochemical assessment for the diagnosis of myocarditis in the majority of cases evaluated. We report evidence suggesting an extremely low frequency of viral myocarditis that has also been associated with unclear therapeutic implications. These two key factors strongly point towards the use of an endomyocardial biopsy to irrefutably reach a diagnosis of viral myocarditis in the context of COVID-19.

Myocardial extracellular volume assessment at CT in hospitalized COVID-19 patients with regards to pulmonary embolism.

PURPOSE: To evaluate myocardial status through the assessment of extracellular volume (ECV) calculated at computed tomography (CT) in patients hospitalized for novel coronavirus disease (COVID-19), with regards to the presence of pulmonary embolism (PE) as a risk factor for cardiac dysfunction. METHOD: Hospitalized patients with COVID-19 who underwent contrast-enhanced CT at our institution were retrospectively included in this study and grouped with regards to the presence of PE. Unenhanced and portal venous phase scans were used to calculate ECV by placing regions of interest in the myocardial septum and left ventricular blood pool. ECV values were compared between patients with and without PE, and correlations between ECV values and clinical or technical variables were subsequently appraised. RESULTS: Ninety-four patients were included, 63/94 of whom males (67%), with a median age of 70 (IQR 56-76 years); 28/94 (30%) patients presented with PE. Patients with PE had a higher myocardial ECV than those without (33.5%, IQR 29.4-37.5% versus 29.8%, IQR 25.1-34.0%; p = 0.010). There were no correlations between ECV and patients' age (p = 0.870) or sex (p = 0.122), unenhanced scan voltage (p = 0.822), portal phase scan voltage (p = 0.631), overall radiation dose (p = 0.569), portal phase scan timing (p = 0.460), and contrast agent dose (p = 0.563). CONCLUSIONS: CT-derived ECV could help identify COVID-19 patients at higher risk of cardiac dysfunction, especially when related to PE, to potentially plan a dedicated, patient-tailored clinical approach.

Cardiovascular aspects of COVID-19.

Coronavirus disease 2019 (COVID-19) is primarily a pulmonary disease, but also affects the cardiovascular system in multiple ways. In this review, we will summarise and put into perspective findings and debates relating to the diverse aspects of cardiovascular involvement of COVID-19. We will review evidence for the role of the renin-angiotensin-aldosterone system (RAAS), the risk of pre-existing cardiovascular disease in COVID-19 susceptibility and course, and the mechanism of acute and long-term myocardial injury. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses membrane-bound angiotensin converting-enzyme-2 (ACE2) as a receptor for cell entry. ACE2 is part of an important counter-regulatory circuit antagonising the harmful effects of angiotensin II on lung and heart. Modulation of ACE2 may therefore affect disease susceptibility and disease course. However, observational clinical studies and one randomised trial have so far not yielded evidence for harmful or beneficial effects of blockers of the RAAS during COVID-19. Age, gender, and multi-morbidity all increase susceptibility to SARS-CoV-2. In contrast, pre-existing cardiovascular diseases do so only minimally, but they may aggravate the disease course. Direct SARS-CoV-2 infection of the heart tissue and myocytes is rare. Nevertheless, COVID-19 may lead to myocarditis-like acute cardiac injury, characterised by myocardial oedema, but lacking extensive myocyte loss and lymphocytic infiltration. Independent of this, increases in cardiac biomarkers (troponin, N-terminal pro-brain natriuretic peptide, D-dimer) are frequent, especially in the phase of severe systemic inflammation and acute respiratory distress syndrome, and quantitatively associated with poor outcome. The pulmonary infection may result initially in right ventricular dysfunction, but in cases with severe systemic infection hypoxia, hyperinflammation and cytokine storm heart failure may eventually ensue. Unlike other infections and inflammatory states, COVID-19 does not appear to trigger acute coronary syndromes. In children, even mild COVID-19 can induce a multisystem inflammatory syndrome with Kawasaki-like symptoms frequently accompanied by cardiogenic shock.

Rhythm and conduction complications after COVID-19 infection in physiological hypertrophy of myocardium (athlete's heart).

The term 'athletic heart syndrome' (AHS) is used to describe specific circulatory and morphological changes in individuals who participate in sports competitions. The syndrome is characterized by normal cardiac function and reversible myocardial remodelling.The incidence and severity of the post-COVID-19 cardiac pathology in active athletes are so far unclear. One of the complications involving the heart is myocarditis. We present a case of a 23-year-old rower after having a moderate COVID-19 infection. Electrocardiograms showed evidence of a shift in conduction and rhythm disturbances ranging from Group 1 (normal ECG findings) to Group 2 (abnormal ECG findings) on the background of an AHS. Echocardiography (with new methods of evaluating deformity - Global Longitudinal Strain) revealed an area with mildly reduced left ventricular deformity around the apex. To assess the subtle alterations in the myocardium, magnetic resonance imaging was used and focal myocarditis was detected. In our patient, considering the degree of severity of his COVID-19 infection - a moderate one, a decision was taken to perform a clinical and instrumental reassessment of his cardiovascular complications 6 months after the infection.This clinical case presents two substantial issues. First, is the AHS more susceptible to rhythm and conduction disturbances after a COVID-19 infection than that of a person who does not actively participate in sports? Second, what the reversibility or the definitive nature of these disturbances is, and how this impacts the prognosis associated with an active sporting activity.

Diagnosis and Treatment of Acute Myocarditis: A Review.

Importance: Acute myocarditis, defined as a sudden inflammatory injury to the myocardium, affects approximately 4 to 14 people per 100 000 each year globally and is associated with a mortality rate of approximately 1% to 7%. Observations: The most common causes of myocarditis are viruses, such as influenza and coronavirus; systemic autoimmune disorders, such as systemic lupus erythematosus; drugs, such as immune checkpoint inhibitors; and vaccines, including smallpox and mRNA COVID-19 vaccines. Approximately 82% to 95% of adult patients with acute myocarditis present with chest pain, while 19% to 49% present with dyspnea, and 5% to 7% with syncope. The diagnosis of myocarditis can be suggested by presenting symptoms, elevated biomarkers such as troponins, electrocardiographic changes of ST segments, and echocardiographic wall motion abnormalities or wall thickening. Cardiac magnetic resonance imaging or endomyocardial biopsy are required for definitive diagnosis. Treatment depends on acuity, severity, clinical presentation, and etiology. Approximately 75% of patients admitted with myocarditis have an uncomplicated course, with a mortality rate of approximately 0%. In contrast, acute myocarditis that is complicated by acute heart failure or ventricular arrhythmias is associated with a 12% rate of either in-hospital mortality or need for heart transplant. Approximately 2% to 9% of patients have hemodynamic instability, characterized by inability to maintain adequate end-organ perfusion, and require inotropic agents, or mechanical circulatory devices, such as extracorporeal life support, to facilitate functional recovery. These patients have an approximately 28% rate of mortality or heart transplant at 60 days. Immunosuppression (eg, corticosteroids) is appropriate for patients who have myocarditis characterized by eosinophilic or giant cell myocardial infiltrations or due to systemic autoimmune disorders. However, the specific immune cells that should be targeted to improve outcomes in patients with myocarditis remain unclear. Conclusions and Relevance: Acute myocarditis affects approximately 4 to 14 per 100 000 people per year. First-line therapy depends on acuity, severity, clinical presentation, and etiology and includes supportive care. While corticosteroids are often used for specific forms of myocarditis (eg, eosinophilic or giant cell infiltrations), this practice is based on anecdotal evidence, and randomized clinical trials of optimal therapeutic interventions for acute myocarditis are needed.

Myocarditis: causes, mechanisms, and evolving therapies.

INTRODUCTION: Myocarditis is a severe lymphocyte-mediated inflammatory disorder of the heart, mostly caused by viruses and immune checkpoint inhibitors (ICIs). Recently, myocarditis as a rare adverse event of mRNA vaccines for SARS-CoV-2 has caused global attention. The clinical consequences of myocarditis can be very severe, but specific treatment options are lacking or not yet clinically proven. AREAS COVERED: This paper offers a brief overview of the biology of viruses that frequently cause myocarditis, focusing on mechanisms important for viral entry and replication following host infection. Current and new potential therapeutic targets/strategies especially for viral myocarditis are reviewed systematically. In particular, the immune system in myocarditis is dissected with respect to infective viral and non-infective, ICI-induced myocarditis. EXPERT OPINION: Vaccination is an excellent emerging preventative strategy for viral myocarditis, but most vaccines still require further development. Anti-viral treatments that inhibit viral replication need to be considered following viral infection in host myocardium, as lower viral load reduces inflammation severity. Understanding how the immune system continues to damage the heart even after viral clearance will define novel therapeutic targets/strategies. We propose that viral myocarditis can be best treated using a combination of antiviral agents and immunotherapies that control cytotoxic T cell activity.

Myocardial Tissue Characterization in Cardiac Magnetic Resonance Studies of Patients Recovering From COVID-19: A Meta-Analysis.

Background Meta-analysis can identify biological factors that moderate cardiac magnetic resonance myocardial tissue markers such as native T1 (longitudinal magnetization relaxation time constant) and T2 (transverse magnetization relaxation time constant) in cohorts recovering from COVID-19 infection. Methods and Results Cardiac magnetic resonance studies of patients with COVID-19 using myocardial T1, T2 mapping, extracellular volume, and late gadolinium enhancement were identified by database searches. Pooled effect sizes and interstudy heterogeneity (I2) were estimated with random effects models. Moderators of interstudy heterogeneity were analyzed by meta-regression of the percent difference of native T1 and T2 between COVID-19 and control groups (%ΔT1 [percent difference of the study-level means of myocardial T1 in patients with COVID-19 and controls] and %ΔT2 [percent difference of the study-level means of myocardial T2 in patients with COVID-19 and controls]), extracellular volume, and the proportion of late gadolinium enhancement. Interstudy heterogeneities of %ΔT1 (I2=76%) and %ΔT2 (I2=88%) were significantly lower than for native T1 and T2, respectively, independent of field strength, with pooled effect sizes of %ΔT1=1.24% (95% CI, 0.54%-1.9%) and %ΔT2=3.77% (95% CI, 1.79%-5.79%). %ΔT1 was lower for studies in children (median age: 12.7 years) and athletes (median age: 21 years), compared with older adults (median age: 48 years). Duration of recovery from COVID-19, cardiac troponins, C-reactive protein, and age were significant moderators for %ΔT1 and/or %ΔT2. Extracellular volume, adjusted by age, was moderated by recovery duration. Age, diabetes, and hypertension were significant moderators of the proportion of late gadolinium enhancement in adults. Conclusions T1 and T2 are dynamic markers of cardiac involvement in COVID-19 that reflect the regression of cardiomyocyte injury and myocardial inflammation during recovery. Late gadolinium enhancement and to a lesser extent extracellular volume, are more static biomarkers moderated by preexisting risk factors linked to adverse myocardial tissue remodeling.

Different Types of Myocardial Injury due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Variant.

Coronavirus disease 2019 (COVID-19) associated myocardial injury was caused by various mechanisms. We herein describe 2 cases presenting different types of myocardial injury due to Omicron variant. In both patients, diffuse reduced left ventricular (LV) wall motion in transthoracic echocardiography, electrocardiographic abnormality, and elevated myocardial enzymes were demonstrated. In addition, cardiovascular magnetic resonance (CMR) findings fulfilled the 2018 Lake Louise Criteria (LLC) for myocarditis. However, histological findings in 1 patient showed inflammatory cell infiltration with myocyte degeneration, while those in the other showed interstitial edema without inflammatory cell infiltration. Histological findings were crucial for a differential diagnosis of myocardial injury due to Omicron variant.

ANALYSIS OF CLINICAL AND FUNCTIONAL INDICES OF CARDIOVASCULAR SYSTEM IN POST-COVID-19 EMERGENCY WORKERS OF THE CHORNOBYL ACCIDENT. / ANALIZ KLINIKO/FUNKTsIONAL'NYKh POKAZNYKIV SERTsEVO-SUDYNNOÏ SYSTEMY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ AVARIÏ PISLIa PERENESENOGO COVID-19.

OBJECTIVE: to determine which changes of cardiovascular system clinical, and structural, and functional state in emergency workers (EW) of the accident at the Chornobyl nuclear power plant (CNNP) can be associated with COVID-19 they suffered from and not with the natural progression of coronary heart disease (CHD). MATERIALS AND METHODS: The study included 16 male EW who fell ill with mild and medium-severe COVID-19 (EWC group) in 2020-2021, which was confirmed by a PCR test (polymerase chain reaction). All these patients were observed in the NRCRM cardiology department before infection with the coronavirus. The comparison group consisted of 32 EW who did not suffer from COVID-19 and their age and examination dates corresponded to EWC. General clinical, laboratory, statistical methods and Doppler echocardiography were used for patients examination. RESULTS: In the post-covid period, EW-C observed a worsening of CHD clinical course, which consisted in an increase in the number of patients with severe functional class angina pectoris, with ventricular and supraventricular extrasystoles, as well as with more severe heart failure (HF). Since similar changes in the state of the cardiovascular system were found among EW who did not suffer from COVID-19, they can be attributed to the natural progression of CHD. In the EW-C group, there was an increase in the number of patients with atrial fibrillation (AF) by 4 times (up 37.5 %), while in the comparison group EW only by 1.1 times (up 3.1 %). The progression of CHD and HF in the examined patients was accompanied by an increase in the end-diastolic and end-systolic volumes of the left ventricle and the mass of the myocardium, the severity of which was not significantly different in patients with and without COVID-19. The number of post-covid patients with reduced ejection fraction (EF) during examination after COVID-19 increased by 31.3 %, and in the group of EW, which were examined at the same time, by 6.32 %. CONCLUSIONS: A significant increase in the number of patients with AF and a reduced EF in the EW-C compared with the EW can be attributed to the results of the SARS-CoV-2 virus influence on cardiovascular system.

Abnormal myocardial enzymes in the prediction of mortality and hypertension in COVID-19 patients: a retrospective study.

This study aims to determine the differences in myocardial enzymes in COVID-19 patients with and without hypertension. A total of 130 patients with COVID-19 in Yunmeng County People's Hospital were analyzed. The clinical manifestations and laboratory indicators were collected and analyzed. We found that COVID-19 patients with hypertension had higher mortality rate, greater age, and higher rates of basic disease such as diabetes than patients without hypertension. The γ-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), albumin/globulin (A/G), Ca, Mg, lactate dehydrogenase (LDH), and α-hydroxybutyric-dehydrogenase (α-HBD) levels in COVID-19 patients with hypertension were higher than in COVID-19 patients without hypertension. We found that the predictive effect of the creatine kinase isoenzyme (CK-MB), LDH-L, and α-HBD levels in the COVID-19 patients without hypertension were higher than in COVID-19 patients with hypertension. We used the ROC curve model to predict whether patients would have hypertension, and we found that CK-MB, LDH-L and HBD parameters could distinguish the COVID-19 patients with hypertension and non-hypertension, and could predict the mortality of COVID-19 patients.

Role of cardiovascular magnetic resonance imaging in COVID-19 recovered patients: A short-term follow-up study.

OBJECTIVE: Cardiac involvement in recovered COVID-19 patients assessed by cardiac magnetic resonance imaging (MRI). METHODS: Subjects recently recovered from COVID-19 and with an abnormal left ventricular global longitudinal strain were enrolled. Cardiac MRI in all the enrolled subjects was done at baseline (within 30-90 days following recovery from COVID-19) with a follow-up scan at 6 months in individuals with an abnormal baseline scan. Additionally, 20 age-and sex-matched individuals were enrolled as healthy controls (HCs). RESULTS: All the 30 enrolled subjects were symptomatic during active COVID-19 disease and were categorized as mild: 11 (36.7%), moderate: 6 (20%), and severe: 13 (43.3%). Of the 30 patients, 16 (53.3%) had abnormal CMR findings. Myocardial edema was reported in 12 (40%) patients while 10 (33.3%) had late gadolinium enhancement (LGE). No difference was observed in terms of conventional left ventricular (LV) parameters; however, COVID-19-recovered patients had significantly lower right ventricular (RV) ejection fraction, RV stroke volume, and RV cardiac index compared to HCs. Follow-up scan was abnormal in 4/16 (25%) with LGE persisting in three patients (who had severe COVID-19 [3/4;75%]). Subjects with severe COVID-19 had a greater frequency of LGE (53.8%) and myocardial edema (61.5%) as compared to mild and moderate cases. Myocardial T1 (1284 ± 43.8 ms vs. 1147.6 ± 68.4 ms; p < .0001) and T2 values (50.8 ± 16.7 ms vs. 42.6 ± 3.6 ms; p = .04) were significantly higher in post COVID-19 subjects compared to HCs. Similarly, T1 and T2 values of severe COVID-19 patients were significantly higher compared to mild and moderate cases. CONCLUSIONS: An abnormal CMR was seen in half of the recovered patients with persistent abnormality in one-fourth at 6 months. Our study suggests a need for closer follow-up among recovered subjects in order to evaluate for long-term cardiovascular sequelae. COVID-19 causes structural changes in the myocardium in a small segment of patients with partial spontaneous resolution.

Protection of zero-valent iron nanoparticles against sepsis and septic heart failure.

BACKGROUND: Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. RESULTS: NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. CONCLUSIONS: The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury.