Acute cardiac side effects after COVID-19 mRNA vaccination, a case series

Background: Since development and approval of the world´s first mRNA vaccines, created under pressure of the global pandemic caused by SARS-CoV-2, potential side effects have naturally been a much-debated topic. Vaccination may be one, if not the only way out of the pandemic claiming more than 4 million deaths worldwide to date. Potential side effects from vaccination have long been controversial, and case reports of fatal side effects have been published. Therefore, data are needed to identify persons being at high risk for potential side effects. Until September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© in young adults were registered by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©).Patients and Methods: Eight patients between 13-56 years of age, vaccinated with mRNA vaccine either BNT162b2 or mRNA-1273 between January and August 2021 developed cardiac side effects shortly after either their first or second vaccination. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after onset of symptoms and investigated further in severe cases. Symptoms were defined as dyspnea, chest pain, cardiac arrhythmia as determined by electrocardiography.Results: Eight patients (five males and three females) developed cardiac symptoms compatible with myocarditis according to CDC criteria shortly after SARS-CoV-2 mRNA vaccination. Three patients (two males, one female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within seven days after symptom onset Conclusion: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

Carfilzomib Treatment Causes Molecular and Functional Alterations of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes

Background Anticancer therapies have significantly improved patient outcomes; however, cardiac side effects from cancer therapies remain a significant challenge. Cardiotoxicity following treatment with proteasome inhibitors such as carfilzomib is known in clinical settings, but the underlying mechanisms have not been fully elucidated. Methods and Results Using human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) as a cell model for drug‐induced cytotoxicity in combination with traction force microscopy, functional assessments, high‐throughput imaging, and comprehensive omic analyses, we examined the molecular mechanisms involved in structural and functional alterations induced by carfilzomib in hiPSC‐CMs. Following the treatment of hiPSC‐CMs with carfilzomib at 0.01 to 10 µmol/L, we observed a concentration‐dependent increase in carfilzomib‐induced toxicity and corresponding morphological, structural, and functional changes. Carfilzomib treatment reduced mitochondrial membrane potential, ATP production, and mitochondrial oxidative respiration and increased mitochondrial oxidative stress. In addition, carfilzomib treatment affected contractility of hiPSC‐CMs in 3‐dimensional microtissues. At a single cell level, carfilzomib treatment impaired Ca 2+ transients and reduced integrin‐mediated traction forces as detected by piconewton tension sensors. Transcriptomic and proteomic analyses revealed that carfilzomib treatment downregulated the expression of genes involved in extracellular matrices, integrin complex, and cardiac contraction, and upregulated stress responsive proteins including heat shock proteins. Conclusions Carfilzomib treatment causes deleterious changes in cellular and functional characteristics of hiPSC‐CMs. Insights into these changes could be gained from the changes in the expression of genes and proteins identified from our omic analyses.

742 Myocarditis after SARS-CoV-2 vaccine: is that so simple?

SARS-CoV-2 vaccination is associated with potential side effects, particularly following second vaccine dose. Recent case series have reported a potential association between SARS-CoV-2 vaccination and acute myocarditis, predominantly in young males. We hereby describe a previously healthy 17-year-old man, with no past cardiac history, who presented to the emergency department with persistent chest pain and fever (up to 38 °C). The patient had received the first dose of Cominarty (BioNTech/Pfizer) vaccine 10 days before symptom onset and reported flu-like symptoms and conjunctivitis involving both eyes one week before administration of the first vaccine dose. On that occasion, no COVID test was performed and the patient was treated with anti-inflammatory drugs and antibiotic eye drops. On admission, laboratory tests were performed (Troponin-I Δ 19 500–23 270 ng/l. CRP 23 mg/dl, ESR 43 s, WBC 17 570 cell/mm3) as well as COVID-19 PCR, Serological tests and Autoimmune disorders panel all resulting negative. CT coronary angiogram did not reveal any spontaneous coronary artery dissection or anomalous origin of coronary arteries and Calcium Score was 0. Transthoracic echocardiography showed a depressed LVEF (36%) with concomitant posterior and inferior wall as well as posterior and anterior basal interventricular septum hypokinesia. Endomyocardial biopsy revealed multifocal lymphocytic myocarditis with sub-endomyocardial and interstitial fibrosis. CMR was also performed (1-week after presentation) demonstrating mildly depressed systolic function (LVEF 47%), with hypokinesia of the posterior and inferior wall, increased signal intensity on T2 maps (58 ms, n.v. <55 ms), prolonged native T1 values (1083 ms, n.v. <1030 ms) as well as subepicardial and intramyocardial LGE enhancement of infero-lateral segments reflecting intercellular fibrosis. Thereafter, the patient was discharged with medical therapy including ACE-inhibitor, colchicine, and ibuprofen. Given the close proximity between SARS-CoV-2 vaccine administration and the absence of other predisposing conditions, the aetiology of myocarditis was attributed to the vaccine. In addition, as the patient suffered from flu-like symptoms and conjunctivitis 1 week before the vaccine, a previous paucisymptomatic SARS-CoV-2 infection was suspected and anti-SARS-Coronavirus Nucleocapsid Protein antibody test revealed high antibody levels with low IgG avidity. Given that myocarditic symptoms evolved after complete Sars-Cov2 symptom resolution, our first hypothesis is that the infection is unlikely to be the cause of acute myocarditis in this patient. Indeed, current literature on COVID-related myocarditis reports close temporal association between respiratory symptoms and myocarditis onset. In support to our hypothesis, recent trials have reported that myocarditis more frequently occurs following administration of mRNA vaccines especially in male adolescents and young adults like our patient. However, cardiac side effects typically occur after full vaccination and symptoms appear within three days following the second dose, which does not fully apply to this case. Notwithstanding this, more recent studies have reported myocarditis even after first vaccination dose in patients with previous COVID-19 infection, analogously to the case described. This case suggests a complex interaction between immunological factors and covid infection/vaccination with potential significant implications on the cardiovascular system. From current literature, much uncertainty remains regarding time interval criteria for reliable post-vaccination myocarditis diagnosis, hence large-scale clinical trials are needed to address this issue.

The Advantages and Disadvantages of Prokinetics

Prokinetics are medications that enhance gastrointestinal contractility; they improve the symptoms of patients with delayed gastrointestinal motility. Prokinetics have conventionally been used to stimulate gastrointestinal propulsion and to treat symptoms correlated with motility problems, including gastroparesis and constipation. 5-Hydroxytryptamine receptor 4 (5-HT4) agonists, such as cisapride, very effectively increased human gastrointestinal tract motility. However, cisapride sometimes induced serious tachyarrhythmia; the drug was thus withdrawn from the market. Thereafter, many prokinetics have been developed to treat delayed gastrointestinal motility. However, some exhibit serious side-effects. Recently, a new, highly selective serotonin receptor agonist, prucalopride, has been introduced; there is as yet no evidence of serious cardiac side- effects. The drug has been approved by the Food and Drug Administration to treat chronic constipation. Thus, recently introduced, highly selective agents appear to show promise as treatments for gastrointestinal dysmotility; there seem to be no serious side-effects.

Cardiac monitoring in memory clinics: national survey of UK practice

Aims and method People diagnosed with dementia are often started on acetylcholinesterase inhibitors (AChEIs). As AChEIs can be associated with cardiac side-effects, an electrocardiogram (ECG) is sometimes requested before treatment. Previous work has suggested there is little consensus as to when or how ECGs should be obtained. This can create inconsistent practice, with patient safety, economic and practical repercussions. We surveyed 305 UK memory clinic practitioners about prescribing practice. Results More than 84% of respondents completed a pulse and cardiac history before prescribing AChEIs. Opinion was divided as to who should fund and conduct ECGs. It was believed that obtaining an ECG causes patients inconvenience and delays treatment. Despite regularly interpreting ECGs, 76% of respondents did not update this clinical skill regularly. Clinical implications The variation in practice observed has service-level and patient implications and raises potential patient safety concerns. Implementing national guidelines or seeking novel ways of conducting cardiac monitoring could help standardise practice.

A review of COVID-19 vaccination and the reported cardiac manifestations

In Singapore, 9.03 million doses of the mRNA COVID-19 vaccines by Pfizer-BioNTech and Moderna have been administered, and 4.46 million people are fully vaccinated. An additional 87,000 people have been vaccinated with vaccines in World Health Organization’s Emergency Use Listing. The aim of this review is to explore the reported cardiac adverse events associated with different types of COVID-19 vaccines. 42 studies that reported cardiac side effects after COVID-19 vaccination were included in this study. Reported COVID-19 vaccine-associated cardiac adverse events were mainly myocarditis and pericarditis, most commonly seen in adolescent and young adult male individuals after mRNA vaccination. Reports of other events such as acute myocardial infarction, arrhythmia and stress cardiomyopathy were rare. Outcomes of post-vaccine myocarditis and pericarditis were good. Given the good vaccine efficacy and the high number of cases of infection, hospitalisation and death that could potentially be prevented, COVID-19 vaccine remains of overall benefit, based on the current available data.

Mitochondrial Transplantation: Is It a Feasible Therapy to Prevent the Cardiorenal Side Effects of Cisplatin?

Mitochondrial transplantation (MT) is a new experimental approach that has demonstrated positive results reverting mitochondrial alterations in cardiac and kidney dysfunction mainly mediated by oxidative stress. On the other hand, cisplatin is an effective and widely used antineoplastic drug in treating several cancers; however, cisplatin has notorious side effects in different organs, such as the heart, kidneys, liver, and brain; the kidney being one of the most affected. The genitourinary system is the principal excretion pathway of cisplatin, since it is removed from the blood primarily by glomerular filtration and tubular secretion, and it may cause a sudden reduction in the renal function (acute kidney injury “AKI”), in part, by inducing mitochondrial dysfunction and the consequent oxidative stress in the tubular segment. In addition, AKI may associate with cardiac alterations, as occurs in acute cardiorenal syndrome. Due to the high prevalence of renal and cardiac side effects produced by cisplatin, here we discuss the possible use of MT as a novel therapy that could protect tissues by alleviating mitochondrial dysfunction and reducing reactive oxygen species (ROS) production.

Electrocardiography abnormality in a suicide attempt with levetiracetam

We present a case of suicide attempt with levetiracetam (LEV) in an epilepsy patient. Multifocal ventricular contractions were observed together with bradycardia in this patient due to LEV overdose. Reported patient of LEV overdose in the literature rarely show electrocardiography findings. Although LEV is less toxic than other antiseizure medications, clinicians should be aware of its potential cardiac side effects.