Myocardial Injury and Altered Gene Expression Associated With SARS-CoV-2 Infection or mRNA Vaccination.

SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2, followed by internalization. COVID-19 mRNA vaccines are RNA sequences that are translated into Spike protein, which follows the same ACE2-binding route as the intact virion. In model systems, isolated Spike protein can produce cell damage and altered gene expression, and myocardial injury or myocarditis can occur during COVID-19 or after mRNA vaccination. We investigated 7 COVID-19 and 6 post-mRNA vaccination patients with myocardial injury and found nearly identical alterations in gene expression that would predispose to inflammation, coagulopathy, and myocardial dysfunction.

Utility of exercise testing to assess athletes for post COVID-19 myocarditis.

Purpose: This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection. Methods: We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days. Results: We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2max, left ventricular ejection fraction and GLS were similar between those with or without myocardial involvement. No adverse events were reported in the 169 athletes cleared to exercise at a median follow-up of 148 (IQR108,211) days. Patients who were initially restricted from exercise had no adverse sequelae and were cleared to resume training between 3 and 12 months post diagnosis. Conclusions: Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection.

The Pathogenesis and Long-Term Consequences of COVID-19 Cardiac Injury.

The mechanisms of coronavirus disease-2019 (COVID-19)-related myocardial injury comprise both direct viral invasion and indirect (hypercoagulability and immune-mediated) cellular injuries. Some patients with COVID-19 cardiac involvement have poor clinical outcomes, with preliminary data suggesting long-term structural and functional changes. These include persistent myocardial fibrosis, edema, and intraventricular thrombi with embolic events, while functionally, the left ventricle is enlarged, with a reduced ejection fraction and new-onset arrhythmias reported in a number of patients. Myocarditis post-COVID-19 vaccination is rare but more common among young male patients. Larger studies, including prospective data from biobanks, will be useful in expanding these early findings and determining their validity.

Cardiac magnetic resonance in recovering COVID-19 patients. Feature tracking and mapping analysis to detect persistent myocardial involvement.

BACKGROUND: Post-COVID-19 patients may incur myocardial involvement secondary to systemic inflammation. Our aim was to detect possible oedema/diffuse fibrosis using cardiac magnetic resonance imaging (CMR) mapping and to study myocardial deformation of the left ventricle (LV) using feature tracking (FT). METHODS: Prospective analysis of consecutively recruited post-COVID-19 patients undergoing CMR. T1 and T2 mapping sequences were acquired and FT analysis was performed using 2D steady-state free precession cine sequences. Statistical significance was set to p < 0.05. RESULTS: Included were 57 post-COVID-19 patients and 20 healthy controls, mean age 59 ± 15 years, men 80.7%. The most frequent risk factors were hypertension (33.3%) and dyslipidaemia (36.8%). The contact-to-CMR interval was 81 ± 27 days. LV ejection fraction (LVEF) was 61 ± 10%. Late gadolinium enhancement (LGE) was evident in 26.3% of patients (19.3%, non-ischaemic). T2 mapping values (suggestive of oedema) were higher in the study patients than in the controls (50.9 ± 4.3 ms vs 48 ± 1.9 ms, p < 0.01). No between-group differences were observed for native T1 nor for circumferential strain (CS) or radial strain (RS) values (18.6 ± 3.3% vs 19.2 ± 2.1% (p = 0.52) and 32.3 ± 8.1% vs 33.6 ± 7.1% (p = 0.9), respectively). A sub-group analysis for the contact-to-CMR interval (<8 weeks vs ≥ 8 weeks) showed that FT-CS (15.6 ± 2.2% vs 18.9 ± 2.6%, p < 0.01) and FT-RS (24.9 ± 5.8 vs 33.5 ± 7.2%, p < 0.01) values were lower for the shorter interval. CONCLUSIONS: Post-COVID-19 patients compared to heathy controls had raised T2 values (related to oedema), but similar native T1, FT-CS and FT-RS values. FT-CS and FT-RS values were lower in post-COVID-19 patients undergoing CMR after < 8 weeks compared to ≥ 8 weeks.

Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?

Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.

Cardiac magnetic resonance imaging during the COVID-19 pandemic: A southern Italian single-center experience.

PURPOSE: We aimed to assess the impact of COVID-19 pandemic on cardiac magnetic resonance (CMR) imaging studies performed during the lockdown imposed by the Italian Government from March 2020 to May 2020. MATERIALS AND METHOD: We reviewed the number and the findings of CMR scans performed during the COVID-19 pandemic between March and May 2020 at University of Naples Federico II. The number and the findings of CMR studies acquired in the corresponding months of 2017, 2018 and 2019 were also assessed for direct comparison. RESULTS: A total of 117 CMR studies was considered, including the procedures performed during the pandemic (n = 18) and those performed in the corresponding months of the prior 3 years (n = 99). The number of CMR studies performed during the COVID-19 pandemic was significantly (P < .01) lower compared to the mean number (n = 33) of the procedures performed in the corresponding months of 2017-2019. The percentage of abnormal CMR studies was similar (P = 0.73) during the pandemic (67 %) compared to that found in the corresponding months of 2017-2019 (70 %) suggesting that many abnormal tests were missed due to the lockdown. CONCLUSION: The number of CMR studies was significantly reduced during the COVID-19 pandemic compared to the corresponding period of the previous three years. The lack of difference in the prevalence of abnormal CMR studies between the two study time intervals strongly suggests that many patients with potentially abnormal imaging test have been missed during the pandemic.

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging.

Objectives: This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR). Background: Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients' recovery from COVID-19. Methods: Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post-COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls. Results: Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs. 38.1 ms ± 2.4 vs. 39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively). Conclusions: Cardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.

SARS-CoV-2 Fulminant Myocarditis.

An 18-year-old male without prior medical history developed fulminant myocarditis concomitant to severe COVID-19 pneumonia, which was confirmed using serial cardiac magnetic resonance. This may have important diagnostic, monitoring, and pathogenic implications. (Level of Difficulty: Intermediate.).

A Recovered Case of COVID-19 Myocarditis and ARDS Treated With Corticosteroids, Tocilizumab, and Experimental AT-001.

We describes a case of a critically ill patient with myocarditis and severe acute respiratory distress syndrome related to coronavirus disease-2019. This case highlights management strategies, including the use of corticosteroids, an interleukin-6 inhibitor, and an aldose reductase inhibitor, resulting in complete clinical recovery. (Level of Difficulty: Intermediate.).