Imaging Cardiovascular Inflammation in the COVID-19 Era

Cardiac complications are among the most frequent extrapulmonary manifestations of COVID-19 and are associated with high mortality rates. Moreover, positive SARS-CoV-2 patients with underlying cardiovascular disease are more likely to require intensive care and are at higher risk of death. The underlying mechanism for myocardial injury is multifaceted, in which the severe inflammatory response causes myocardial inflammation, coronary plaque destabilization, acute thrombotic events, and ischemia. Cardiac magnetic resonance (CMR) imaging is the non-invasive method of choice for identifying myocardial injury, and it is able to differentiate between underlying causes in various and often challenging clinical scenarios. Multimodal imaging protocols that incorporate CMR and computed tomography provide a complex evaluation for both respiratory and cardiovascular complications of SARS-CoV2 infection. This, in relation to biological evaluation of systemic inflammation, can guide appropriate therapeutic management in every stage of the disease. The use of artificial intelligence can further improve the diagnostic accuracy of these imaging techniques, thus enabling risk stratification and evaluation of prognosis. The present manuscript aims to review the current knowledge on the possible modalities for imaging COVID-related myocardial inflammation or post-COVID coronary inflammation and atherosclerosis.

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Cardiomyocyte injury following Acute Ischemic Stroke (CORONA-IS): Protocol for a prospective observational cohort study (Preprint)

10.2196/preprints.24186 ◽

2020 ◽

Author(s):

Helena Stengl ◽

Ramanan Ganeshan ◽

Simon Hellwig ◽

Edyta Blaszczyk ◽

Jochen B Fiebach ◽

...

Keyword(s):

Cohort Study ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Symptom Onset ◽

Cardiac Troponin ◽

Myocardial Injury ◽

Underlying Mechanism ◽

Cardiac Complications ◽

Coronary Syndrome ◽

Cerebral Mri

BACKGROUND Elevated cardiac troponin (cTn) indicating cardiomyocyte injury is common after acute ischemic stroke (AIS) and associated with poor functional outcome. Myocardial injury is part of a broad spectrum of cardiac complications that may occur after AIS. Previous studies have shown that in most patients the underlying mechanism of stroke-associated myocardial injury may not be a concomitant acute coronary syndrome. Evidence from animal research, clinical and neuroimaging studies suggest that functional and structural alterations in the central autonomic network leading to stress-mediated neurocardiogenic injury may be a key underlying mechanism (i.e., ‘Stroke-Heart-Syndrome’). However, the exact pathophysiological cascade remains unclear and diagnostic and therapeutic implications are unknown. OBJECTIVE The aim of the Cardiomyocyte injury following Acute Ischemic Stroke (CORONA-IS) study is to quantify autonomic dysfunction and to decipher downstream cardiac mechanisms leading to myocardial injury after AIS. METHODS In this prospective, observational, single-center cohort study, 300 patients with acute ischemic stroke, confirmed via cerebral MRI and presenting within 48h of symptom onset, will be recruited during in-hospital stay. Based on high-sensitivity cardiac troponin levels (hs troponinT, Gen. V, Roche Elecsys®) and corresponding to the fourth universal definition of myocardial infarction, three groups are defined (i.e. ‘no myocardial injury’ [no cTN elevation], ‘chronic myocardial injury’ [stable elevation] and ‘acute myocardial injury’ [dynamic rise/fall pattern]). Each group will include approximately 100 patients. Study patients will receive routine diagnostic care and additionally, 1) 3T cardiovascular MRI and transthoracic echocardiography within 5 days of symptom onset to provide myocardial tissue characterization and assess cardiac function, 2) 20-minute high-resolution ECG-recording for analysis of cardiac autonomic function, and 3) extensive biobanking. A follow-up for cardiovascular events will be conducted 3 and 12 months after inclusion. RESULTS After a four-month pilot phase, recruitment started in April 2019. We estimate a recruitment period of approximately three years to include 300 patients with complete CMR protocol. CONCLUSIONS Stroke-associated myocardial injury is a common and relevant complication. Our study has the potential to provide a better mechanistic understanding of heart and brain interaction in the setting of acute stroke. This will be essential to develop algorithms for recognizing patients at risk and refine diagnostic and therapeutic procedures. CLINICALTRIAL Clinicaltrials.gov NCT03892226

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Myocardial Injury after Noncardiac Surgery and Perioperative Atrial Fibrillation

Canadian Journal of General Internal Medicine ◽

10.22374/cjgim.v16isp1.530 ◽

2021 ◽

Vol 16 (SP1) ◽

pp. 18-26

Author(s):

Flavia Borges ◽

Sandra Ofori ◽

Maura Marcucci

Keyword(s):

Atrial Fibrillation ◽

Myocardial Injury ◽

Prediction Models ◽

Controlled Trial ◽

Noncardiac Surgery ◽

Prise En Charge ◽

Individual Risk ◽

Cardiac Complications ◽

Risk Of Death ◽

Fibrillation Auriculaire

One in 60 patients who undergo major noncardiac surgery dies within 30 days following surgery. The most common cause is cardiac complications, of which myocardial injury after noncardiac surgery (MINS) and perioperative atrial fibrillation (POAF) are common, affecting about 18 and 11% of adults, respectively, after noncardiac surgery. Patients who suffer MINS are at a higher risk of death compared to patients without MINS. Similarly, patients who develop POAF are at a higher risk of stroke and death compared to patients who do not. Most patients who suffer MINS are asymptomatic, and its diagnosis is not possible without routine troponin monitoring. Observational studies support the use of statins and aspirin in the management of patients with MINS. The only randomized controlled trial to date that has specifically addressed the management of MINS was the MANAGE trial that demonstrated the efficacy and safety of intermediate dose dabigatran in this population. There are no specific prediction models for POAF and no randomised controlled trial evidence to guide the specific management of POAF. Management guidelines in the acute period follow the management of nonoperative atrial fibrillation. The role of long-term anticoagulation in this population is still uncertain and should be guided by a shared care decision model with the patient, and with consideration of the individual risk for stroke balanced against the risk of bleeding. In this review, we present a case-based approach to the detection, prognosis, and management of MINS and POAF based on the existing evidence. RÉSUMÉUn patient sur 60 qui subit une intervention chirurgicale majeure non cardiaque meurt dans les 30 jours suivant l’opération. La cause la plus fréquente est celle des complications cardiaques, dont les lésions myocardiques après une chirurgie non cardiaque (LMCNC) et la fibrillation auriculaire périopératoire (FAPO) sont courantes et touchent respectivement environ 18 et 11 % des adultes après une chirurgie non cardiaque. Les patients présentant des LMCNC sont exposés à un risque plus élevé de décès que les patients qui ne présentent pas de LMCNC. De même, les patients chez qui on voit apparaître une FAPO ont un risque plus élevé d’accident vasculaire cérébral et de décès que ceux qui ne connaîtront pas cette complication. La plupart des patients atteints de LMCNC sont asymptomatiques, et il est impossible d’établir un diagnostic sans surveiller régulièrement la troponine. Des études d’observation appuient l’utilisation des statines et de l’aspirine dans la prise en charge des patients atteints de LMCNC. À ce jour, le seul essai contrôlé randomisé qui s’est penché précisément sur le traitement des LMCNC est l’essai MANAGE qui a démontré l’efficacité et l’innocuité du dabigatran à dose intermédiaire chez cette population. Il n’existe aucun modèle de prédiction précis pour la FAPO ni aucune donnée probante provenant d’essais contrôlés randomisés pour orienter précisément son traitement. Les lignes directrices concernant la prise en charge au cours de la période aiguë suivent celles de la prise en charge de la fibrillation auriculaire non liée à une opération. Le rôle de l’anticoagulation à long terme chez cette population est encore incertain et devrait être guidé par un modèle de prise de décision partagée avec le patient et tenir compte du risque individuel d’accident vasculaire cérébral par rapport à celui d’hémorragie. Dans cette revue, nous présentons une approche fondée sur des cas pour la détection, le pronostic et le traitement des LMCNC et de la FAPO sur la base des données probantes existantes.

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Human Urinary Kallidinogenase (HUK) Alleviates Myocardial Injury in Rats with Coronary Microembolism Through PI3K/Akt/FoxO1 Signaling Pathway.

10.21203/rs.3.rs-1054881/v1 ◽

2021 ◽

Author(s):

Jian Xie ◽

Yunhua Lin ◽

Guoqing Liu ◽

Qingqing Nong ◽

Bingling Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Injury ◽

Histopathological Examination ◽

Specific Inhibitor ◽

Underlying Mechanism ◽

Myocardial Inflammation ◽

Sham Operation ◽

Protective Effects ◽

Sprague Dawley ◽

Cardioprotective Effects

Abstract PurposeCoronary artery microembolization (CME) is a severe clinical complication that can cause myocardial infarction, induce myocardial inflammation and apoptosis, ultimately lead to cardiac dysfunction. Human Urinary Kallidinogenase (HUK), a glycoprotein found in human urine, its role and underlying mechanism in CME are still unclear. Therefore, our goal is to explore the effect of HUK on the PI3K/Akt/FoxO1 axis of CME in rats, determine whether it can restrain myocardial inflammation and apoptosis, and alleviate CME-induced myocardial injury.MethodsWe split 40 Sprague-Dawley (SD) rats into CME, CME + HUK, CME + HUK + LY294002 (CME + HUK + LY), and sham operation groups randomly (10 animals in each group). The dosage of HUK was 0.016 PNA/kg/day. Also, 42μm inert plastic microspheres were injected into the left ventricle of rats to establish the CME model. Notably, rats in the CME+HUK+LY group were injected 10 mg/kg of LY294002 (a particular inhibitor of PI3K) intraperitoneally 30 minutes before modeling. We measured cardiac function 12 hours after the operation. Besides, the serum of myocardial injury biomarkers and myocardial inflammation, as well as apoptosis-related genes were measured, the myocardial histopathological examination was also performed.ResultsOur results indicated that CME induced myocardial inflammation and apoptosis, also caused myocardial infarction. HUK mainly activated PI3K/Akt/FoxO1 signal transduction, effectively reducing myocardial inflammation, apoptosis, and myocardial infarction area and improving CME-induced myocardial injury. In addition, these cardioprotective effects can be reduced by PI3K specific inhibitor LY294002, suggesting that the above protective effects may be related to the process of activation of the PI3K/ Akt /FoxO1 axis.ConclusionOur findings revealed that HUK might restrain myocardial inflammation and apoptosis by activating the PI3K/Akt/FoxO1 axis, thus ameliorating CME-induced myocardial injury.

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Microglia in Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205017666200212155234 ◽

2020 ◽

Vol 17 (1) ◽

pp. 29-43 ◽

Cited By ~ 3

Author(s):

Patrick Süß ◽

Johannes C.M. Schlachetzki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Current Knowledge ◽

Imaging Techniques ◽

Amyloid Β ◽

Disease Stage ◽

Disease Modifying Therapy ◽

Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

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Cardiotoxic effects and myocardial injury: the search for a more precise definition of drug cardiotoxicity

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0566 ◽

2021 ◽

Vol 59 (1) ◽

pp. 51-57

Author(s):

Daniela Maria Cardinale ◽

Martina Zaninotto ◽

Carlo Maria Cipolla ◽

Claudio Passino ◽

Mario Plebani ◽

...

Keyword(s):

Early Detection ◽

Myocardial Injury ◽

Randomized Clinical Trials ◽

Imaging Techniques ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cardiac Imaging Techniques ◽

Ventricular Ejection Fraction ◽

Early Evaluation ◽

Definition Of

AbstractDrug-induced cardiotoxicity is a major clinical problem; cardiotoxic drugs may induce both cardiac dysfunction and myocardial injury. Several recent studies reported that cardiac troponins measured with high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have some concerns about the standard definition of cardiotoxicity, in particular, regarding the early evaluation of chemotherapy cardiotoxicity in cancer patients. Several recent studies using the hs-cTn assay indicate that myocardial injury may precede by some months or years the diagnosis of heart failure (HF) based on the evaluation of left ventricular ejection fraction (LVEF). Accordingly, hs-cTn assay should considered to be a reliable laboratory test for the early detection of asymptomatic or subclinical cardiotoxic damage in patients undergoing cancer chemotherapy. In accordance with the Fourth Universal Definition of Myocardial Infarction and also taking into account the recent experimental and clinical evidences, the definition of drug-cardiotoxicity should be updated considering the early evaluation of myocardial injury by means of hs-cTn assay. It is conceivable that the combined use of hs-cTn assay and cardiac imaging techniques for the evaluation of cardiotoxicity will significantly increase both diagnostic sensitivity and specificity, and also better prevent chemotherapy-related left ventricular (LV) dysfunction and other adverse cardiac events. However, large randomized clinical trials are needed to evaluate the cost/benefit ratio of standardized protocols for the early detection of cardiotoxicity using hs-cTn assay in patients receiving chemotherapy for malignant diseases.

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Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01924-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sanchi Malhotra ◽

Imran Masood ◽

Noberto Giglio ◽

Jay D. Pruetz ◽

Pia S. Pannaraj

Keyword(s):

United States ◽

Differential Diagnosis ◽

Heart Disease ◽

Chagas Disease ◽

Latin American ◽

Current Knowledge ◽

Parasitic Infection ◽

The United States ◽

Cardiac Complications ◽

The U.S

Abstract Background Chagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S. Methods We prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience. Results Of 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture. Conclusions Pediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

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Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

Journal of Clinical Medicine ◽

10.3390/jcm10061214 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1214

Author(s):

Ji Tu ◽

Jose Vargas Castillo ◽

Abhirup Das ◽

Ashish D. Diwan

Keyword(s):

Cervical Myelopathy ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Imaging Techniques ◽

Disease Process ◽

Classification Systems ◽

Molecular Features ◽

Formidable Challenge ◽

Long Term Treatment ◽

Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

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Antimalarial drugs—are they beneficial in rheumatic and viral diseases?—considerations in COVID-19 pandemic

Clinical Rheumatology ◽

10.1007/s10067-021-05805-5 ◽

2021 ◽

Author(s):

Bogna Grygiel-Górniak

Keyword(s):

Connective Tissue ◽

Viral Infections ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Antiviral Drugs ◽

In Vivo Studies ◽

Viral Diseases ◽

Cardiac Complications

AbstractThe majority of the medical fraternity is continuously involved in finding new therapeutic schemes, including antimalarial medications (AMDs), which can be useful in combating the 2019-nCoV: coronavirus disease (COVID-19). For many decades, AMDs have been widely used in the treatment of malaria and various other anti-inflammatory diseases, particularly to treat autoimmune disorders of the connective tissue. The review comprises in vitro and in vivo studies, original studies, clinical trials, and consensus reports for the analysis, which were available in medical databases (e.g., PubMed). This manuscript summarizes the current knowledge about chloroquine (CQ)/hydroxychloroquine (HCQ) and shows the difference between their use, activity, recommendation, doses, and adverse effects on two groups of patients: those with rheumatic and viral diseases (including COVID-19). In the case of connective tissue disorders, AMDs are prescribed for a prolonged duration in small doses, and their effect is observed after few weeks, whereas in the case of viral infections, they are prescribed in larger doses for a short duration to achieve a quick saturation effect. In rheumatic diseases, AMDs are well tolerated, and their side effects are rare. However, in some viral diseases, the effect of AMDs is questionable or not so noticeable as suggested during the initial prognosis. They are mainly used as an additive therapy to antiviral drugs, but recent studies have shown that AMDs can diminish the efficacy of some antiviral drugs and may cause respiratory, kidney, liver, and cardiac complications.

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Cardiac complications during the active phase of COVID-19: review of the current evidence

Internal and Emergency Medicine ◽

10.1007/s11739-021-02763-3 ◽

2021 ◽

Author(s):

Mohammad Said Ramadan ◽

◽

Lorenzo Bertolino ◽

Tommaso Marrazzo ◽

Maria Teresa Florio ◽

...

Keyword(s):

Myocardial Injury ◽

Myocardial Damage ◽

Active Phase ◽

Mortality Rates ◽

Major Effect ◽

Current Evidence ◽

Cardiac Complications ◽

Published Data ◽

Improving Patient Care ◽

Overall Mortality

AbstractGrowing reports since the beginning of the pandemic and till date describe increased rates of cardiac complications (CC) in the active phase of coronavirus disease 2019 (COVID-19). CC commonly observed include myocarditis/myocardial injury, arrhythmias and heart failure, with an incidence reaching about a quarter of hospitalized patients in some reports. The increased incidence of CC raise questions about the possible heightened susceptibility of patients with cardiac disease to develop severe COVID-19, and whether the virus itself is involved in the pathogenesis of CC. The wide array of CC seems to stem from multiple mechanisms, including the ability of the virus to directly enter cardiomyocytes, and to indirectly damage the heart through systemic hyperinflammatory and hypercoagulable states, endothelial injury of the coronary arteries and hypoxemia. The induced CC seem to dramatically impact the prognosis of COVID-19, with some studies suggesting over 50% mortality rates with myocardial damage, up from ~ 5% overall mortality of COVID-19 alone. Thus, it is particularly important to investigate the relation between COVID-19 and heart disease, given the major effect on morbidity and mortality, aiming at early detection and improving patient care and outcomes. In this article, we review the growing body of published data on the topic to provide the reader with a comprehensive and robust description of the available evidence and its implication for clinical practice.

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Cardiac MRI and Myocardial Injury in COVID-19: Diagnosis, Risk Stratification and Prognosis

Diagnostics ◽

10.3390/diagnostics11010130 ◽

2021 ◽

Vol 11 (1) ◽

pp. 130

Author(s):

Saagar K. Sanghvi ◽

Logan S. Schwarzman ◽

Noreen T. Nazir

Keyword(s):

Risk Stratification ◽

Myocardial Injury ◽

Cardiac Tissue ◽

Contractile Function ◽

Imaging Modality ◽

Acute Myocarditis ◽

Myocardial Inflammation ◽

Critical Data ◽

Non Invasive ◽

Risk Of Exposure

Myocardial injury is a common complication of the COVID-19 illness and is associated with a worsened prognosis. Systemic hyperinflammation seen in the advanced stage of COVID-19 likely contributes to myocardial injury. Cardiac magnetic resonance imaging (CMR) is the preferred imaging modality for non-invasive evaluation in acute myocarditis, enabling risk stratification and prognostication. Modified scanning protocols in the pandemic setting reduce risk of exposure while providing critical data regarding cardiac tissue inflammation and fibrosis, chamber remodeling, and contractile function. The growing use of CMR in clinical practice to assess myocardial injury will improve understanding of the acute and chronic sequelae of myocardial inflammation from various pathological etiologies.

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