To the Editor, We read with interest the article by Peltzer et al. referring to the occurrence of atrial fibrillation and flutter (AF/f) in patients hospitalized with coronavirus disease (COVID‐19). An incidence of 16% was observed, while 60% of this arrhythmia was of new onset. The manifestation of AF/f was followed by high morbidity and mortality, which were further aggravated when markers of cardiac injury and inflammation were present, suggesting an imminent cytokine storm. The study was retrospective; thus, information regarding the therapeutic treatment of AF/f was missing. However, in an illustrated paradigm, the treatment consisted of the administration of amiodarone and digoxin. Digoxin and digitalis are the main clinical representatives of cardiac glycosides (CGS), in uninterrupted use for more than a century, prescribed for controlling heart rate in AF/f. Although beta‐blockers and calcium antagonists seem to obtain preference temporarily, CGS remains of undisputed value when AF/f coexists with low blood pressure and heart failure. Of notice, in the study by Peltzer et al., a large number of patients were under vasopressor support, preventing the use of beta‐ blockers and calcium antagonists. For years, the clinical application of CGS was justified by their ability to suppress Na,K‐ATPase membrane pump, with secondary modulations of Na, K, and Ca intracellular concentrations. Accumulation of Na and Ca with parallel K depletion were considered suitable to explain the dromotropic, chronotropic, and inotropic properties of CGS. However, a recent investigation in the field of oncology revealed unexpected characteristics of CGS related to their ability to transform Na,K‐ATPase into a signaling transducer, capable of suppressing complex intracellular protein machinery. By this action, significant anticancer, antiviral, and anti‐inflammatory effects were obtained in vitro and in vivo. When this data was tested during the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome coronavirus (SARS‐CoV) endemics, the results were more than promising. CGS administration compromised the whole viral cycle, including RNA replication, messenger RNA transcription, host cell translation of proteins, and finally budding of the newly formed viral particles. Similar findings were obtained when CGS were tested in the setting of other DNA and RNA viruses, with implications in COVID‐19 infection. Of further significance were the anti‐inflammatory properties of CGS exerted via Na,K‐ATPase inhibition. Hyperinflammation and cytokine cascade was suppressed in various experimental observations, including the nuclear transcription factor NF‐KB, which, in turn, suppresses a whole series of other proinflammatory factors, such as TNFα, TGFβ, GRO/KC, MCP1, MIP2, IL‐1β, and finally interferon IFNγ. To conclude, CGS with their electrophysiological and immunological properties merit a priority in the armor against COVID‐19, especially when atrial arrhythmias complicate the in‐hospital course.

Novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19] pandemic) attacks the host cells modulating the local renin-angiotensin (RAS) system. Pending a definitive antivirus therapy, Fedson and colleagues propose in their recent article (1) a combination of generic drugs such as statins and angiotensin receptor blockers (ARBs) to prevent catastrophic cellular damage. The proposal could be applicable in a model of heart failure (HF) patients infected by coronavirus. These patients belong to the most vulnerable groups while concentrating in …

Jian et al1Jian L. Yi W. Zhang N. Wen W. Krysko O. Song W.J. et al.Perspective: COVID-19, implications of nasal diseases and consequences for their management.J Allergy Clin Immunol. 2020; 146: 67-69Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar in a recent article refer to the immune reaction of the upper respiratory tract (URT) in patients infected by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 (coronavirus disease 2019 [COVID-19] pandemic). The authors wonder about the consequences of inhaled corticosteroids (ICSs) on immune reaction. We share the queries of Jian et al, from a practical point of view. Since late February 2020, when the COVID-19 outbreak exploded in Greece, emergency departments (EDs) of major hospitals were enrolled in triaging patients with suspicious clinical presentation. Medical staff was called to perform nasopharyngeal and oropharyngeal swabbing, irrespective of specialization, and forwarding the samples for a PCR. Training was offered through educational videos.2Marty F.M. Chen K. Verrill K. How to obtain a nasopharyngeal swab specimen.N Engl J Med. 2020; 382: e76Crossref PubMed Scopus (171) Google Scholar The authors of this letter are going to maintain such a triage during the summer months when a wave of tourists from countries with different prevalence of COVID-19 is going to visit Greece. Pitfalls in performing nasopharyngeal or oropharyngeal swabbing are not negligible. Learning from the experience of previous medical personnel engaged in ED, we focus on an intriguing problem we are going to cope with. Given the pneumonologic character of the hospital and the seasonal allergies, 15% to 25% of patients admitted to the ED are expected to suffer exacerbations of chronic obstructive pulmonary disease, asthma, rhinitis, and rhinosinusitis. Most of them are under chronic or seasonal therapies with ICSs, oral or intranasal. With the URT sprayed by ICSs, we are wondering about the diagnostic accuracy of specimens collected. Asking patients to blow their nose, or postponing the procedure is not feasible, as far as we ignore the washout period needed for an ICS, especially in chronic administration. ICSs are likely to modify the replication of commensal and pathogenic virome in the nasopharynx, oropharynx, and saliva.3Ramakrishnan V.F. Holt J. Nelson L.F. Ir D. Robertson C.E. Frank D.N. Determinants of the nasal microbiome: pilot study of effects of intranasal medication use.Allergy Rhinol. 2018; 9: 1-10Crossref Google Scholar Medical literature regarding the effects of ICSs on pathogenic virome of the URT is scarce. We try to extrapolate data from previous coronavirus epidemics, namely, SARS-CoV, Middle East respiratory syndrome (MERS), and HCoV-229E. ICSs are expected to enhance pathogenic viral replications in the URT, predisposing to subsequent bacterial infection.4Singanayagam A, Johnston SL. Long-term impact of inhaled corticosteroid use in asthma and chronic obstructive pulmonary disease (COPD): review of mechanisms that underlie risks [published online ahead of print 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2019.12.907.Google Scholar This is likely for inhaled cortisone, prednisolone, dexamethasone, and fluticasone. Contrarily, mometasone inhibits the replication of SARS-CoV and HCoV-229E.5Matsuyama S. Kawase M. Nao N. Shirato K. Ujike M. Kamitani W. et al.The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15.bioRxiv. 2020; Google Scholar Similarly, budesonide degrades the virulence of HCoV-229E.6Yamaya M. Nishimura H. Deng X. Sugawara M. Watanabe O. Nomura K. et al.Inhibitory effects of glucopyrronium, formoterol, and budesonide in coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells.Respir Investig. 2020; 58: 155-168Crossref PubMed Scopus (193) Google Scholar Recently, the ICS ciclesonide was found to suppress the replication of SARS-CoV-2, by directly attacking the NSP15 viral endoribonuclease, demonstrating an antiviral function.7Jean S, Ko M, Lee J, Choi I, Byun SY, Park S, et al. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs [published online ahead of print 2020]. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00819-20.Google Scholar Therapies with ICSs modulate the innate defensive mechanisms of the URT, interfering with cytokines, while at the same time perturbate the abundance and replication of commensal and pathogenic viruses.3Ramakrishnan V.F. Holt J. Nelson L.F. Ir D. Robertson C.E. Frank D.N. Determinants of the nasal microbiome: pilot study of effects of intranasal medication use.Allergy Rhinol. 2018; 9: 1-10Crossref Google Scholar,7Jean S, Ko M, Lee J, Choi I, Byun SY, Park S, et al. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs [published online ahead of print 2020]. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00819-20.Google Scholar Depending on the chemical composition of ICSs, the impact on the virome of the URT is unpredictable. With this in mind, swabbing the URT of coronavirus-infected patients under an ICS regimen renders the quality of the viral load collected questionable. Taking alternative specimens from pleural effusions, stools, or even blood is of dubious diagnostic value. With all this scepticism in our minds, we are preparing ourselves to cope with the intricacies of triaging in a COVID-19 era, performing with responsibility the swabbing techniques, ensuring specimens of high diagnostic accuracy. Perspective: COVID-19, implications of nasal diseases and consequences for their managementJournal of Allergy and Clinical ImmunologyVol. 146Issue 1PreviewThe severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused a global health emergency. With increasing numbers of infected people and deaths worldwide reported daily since the beginning of the year, we have to urgently focus on a new pandemic caused by the SARS-CoV-2, a betacoronavirus related to SARS-CoV. We have to urgently learn more about this virus, its ways of transmission to spread infection so fast all over the world, the pathomechanisms involved in human infection and intracellular entry, the consecutive spreading within the body, and finally the factors that determine the difference between a mild or even asymptomatic infection in one and a deadly disease in another patient. Full-Text PDF

Cardiac glycosides have been found to have an anti-viral effect. This was noted in the past during various epidemics including MERS and SARS. It is due to their inhibitory effect on the Na, K-ATPase membrane pump. Furthermore, they exhibit antiinflammatory properties. These preclinical observations may prove useful in further clinical utility of these well-known compounds in the current COVID-19 pandemic.

Geriatrics & Gerontology InternationalVolume 19, Issue 8 p. 840-841 LETTER TO THE EDITOR Neprilysin inhibitors and chest pain perception in acute myocardial infarction Eftychios Siniorakis, Eftychios Siniorakis Department of Cardiology, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this authorSpyridon Arvanitakis, Spyridon Arvanitakis orcid.org/0000-0001-5400-083X Department of Cardiology, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this authorGeorgia Konstantopoulou, Georgia Konstantopoulou Department of Anesthesiology, Pain Relief Clinic, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this authorLouloudia Katechalidou, Louloudia Katechalidou Department of Neurology, Elpis General Hospital, Athens, GreeceSearch for more papers by this authorSotiria Limberi, Sotiria Limberi Department of Cardiology, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this author Eftychios Siniorakis, Eftychios Siniorakis Department of Cardiology, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this authorSpyridon Arvanitakis, Spyridon Arvanitakis orcid.org/0000-0001-5400-083X Department of Cardiology, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this authorGeorgia Konstantopoulou, Georgia Konstantopoulou Department of Anesthesiology, Pain Relief Clinic, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this authorLouloudia Katechalidou, Louloudia Katechalidou Department of Neurology, Elpis General Hospital, Athens, GreeceSearch for more papers by this authorSotiria Limberi, Sotiria Limberi Department of Cardiology, Sotiria Chest Diseases Hospital, Athens, GreeceSearch for more papers by this author First published: 08 August 2019 https://doi.org/10.1111/ggi.13719Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume19, Issue8August 2019Pages 840-841 RelatedInformation

Based on the findings of the emblematic PARADIGM-HF study [...]

BACKGROUND/AIM:Several risk scores can stratify patients with acute heart failure (AHF) at the Emergency Department (ED). Registration of vital signs, such as blood pressure (BP), heart rate (HR) and respiratory rate (RR) upon admission is mandatory. Nevertheless, measurement of RR remains neglected worldwide. PATIENTS AND METHODS:The predictive value of RR in classifying patients with AHF was investigated by processing several vital signs recorded in the ED. RESULTS:HR and RR individually did not discriminate patients according to hospitalization length, Intensive Care Unit (ICU) admittance, mechanical respiratory support or death. The derivative indices, HR:RR and Respiratory Efficacy Index (REFI) (=RR×100/SatO2), differentiated study patients regarding hospitalization length. Receiver operating characteristic curves predicting mortality and ICU admission for REFI and HR:RR revealed high accuracy, sensitivity and specificity for cut-off values of REFI >27 and HR:RR ≥4. CONCLUSION:The RR and its derivative indices are easily accessible vital signs monitored at the ED which merit 'revitalization'.

Pectus excavatum (PEXT) consists of an overgrowth of the chondral region with posterior displacement of the inferior part of the sternum, resulting in a concave chest deformity. Characteristic clinical and imaging findings may occur, depending on the compression that right cardiac chambers suffer, when squeezed between the sternum and the column vertebrae.

BACKGROUND:The clinical manifestations of acute heart failure (AHF) and respiratory infection (RI) frequently overlap in patients presenting with dyspnoea at the emergency department (ED). The neutrophil to lymphocyte (N/L) and platelet to lymphocyte (P/L) ratios have been proposed as diagnostic and prognostic indices in this setting.OBJECTIVE:To evaluate the ability of N/L and P/L ratios to discriminate the cause of dyspnoea in patients admitted with an initial diagnosis of AHF-RI.METHODS:100 consecutive dyspnoeic chronic heart failure (CHF) patients diagnosed as AHF-RI in the ED of Sotiria Chest Diseases General Hospital were monitored for a series of parameters. The diagnostic efficacy of the registered parameters in discriminating the AHF from RI patients was evaluated.RESULTS:The N/L and P/L ratios did not differ statistically depending on the pharmaceutical therapy applied in the study population, with the exception of furosemide and spironolactone-treated patients, who both had higher ratio values. In the AHF patients, only N/L was influenced by the pharmaceutical treatment administered. Patients with higher N/L ratio values were more likely to have RI-triggereddyspnoea (odds ratio, OR=1.35, 95% confidence interval-CI: 0.99-1.42, p=0.047). ROC curve (receiver operating characteristic curve) analysis revealed a significant ability of the N/L ratio to differentiate pure AHF from RI (area under the curve AUC=0.773, p<0.001, cut-off value N/L= 3.15).CONCLUSION:The N/L ratio, a cheap and easily assessed biomarker, warrants further investigation as a potential diagnostic tool for the ED physician facing dyspnoeic CHF patients.

Community acquired pneumonia (CAP) is a frequent triggering factor for decompensation of a chronic cardiac dysfunction, leading to acute heart failure (AHF). Patients with AHF exacerbated by CAP, are often admitted through the emergency department for ICU hospitalization, even though more than half the cases do not warrant any intensive care treatment. Emergency department physicians are forced to make disposition decisions based on subjective criteria, due to lack of evidence-based risk scores for AHF combined with CAP. Currently, the available risk models refer distinctly to either AHF or CAP patients. Extrapolation of data by arbitrarily combining these models, is not validated and can be treacherous. Examples of attempts to apply acuity scales provenient from different disciplines and the resulting discrepancies, are given in this review. There is a need for severity classification tools especially elaborated for use in the emergency department, applicable to patients with mixed AHF and CAP, in order to rationalize the ICU dispositions. This is bound to facilitate the efforts to save both lives and resources.

We thank Dr. T. Kirat and colleagues for their interest in our paper [ [1] Siniorakis E. Arvanitakis S. Tzevelekos P. Panta S. Zampelis C. Aivalioti F. et al. Hypertensive heart disease and bronchodilators: potential left ventricular outflow obstruction. Int. J. Cardiol. 2015; 196: 123-124 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar ]. We described the case of a hypertensive woman who demonstrated a symptomatic left ventricular outflow tract (LVOT) obstruction, while inhaling a nebulized mixture of a beta stimulating and a muscarinic antagonistic bronchodilator. Dr. Kirat et al. [ [2] Kirat T. Köse N. Altun İ. Akin F. Özcan Soylu M. The effects of parasympatheticolytic and sympatheticomimetic nebulization therapy in gradient increase in the left ventricular outflow tract: Do they have the same influence?. Int. J. Cardiol. 2016; 203: 1138-1139 Abstract Full Text Full Text PDF Scopus (1) Google Scholar ] refer to the innervation of normal heart, consisting of sympathomimetic adrenoreceptors and parasympatheticomimetic muscarinic receptors. However, an analogous situation in hypertrophic hearts remains rather unexplored. Cardiac muscarinic receptors appear up- or down-regulated concerning their density and affinity, according to the loading conditions [ [3] Liu Y. Wang S. Wang C. Song H. Han H. Hang P. et al. Upregulation of M3 muscarinic receptor inhibits hypertrophy induced by angiotensin II. J. Transl. Med. 2013; 11: 209 Crossref PubMed Scopus (18) Google Scholar ]. Furthermore, there is a sympathetic-parasympathetic interaction, leading to unpredictable reactions of the vagal drive, when adrenoreceptors are stimulated by beta agonistic bronchodilators [ [4] Olshansky B. Sabbah H. Hauptman P. Colucci W. Parasympathetic nervous system and heart failure: pathophysiology and potential implications for therapy. Circulation. 2008; 118: 863-871 Crossref PubMed Scopus (293) Google Scholar ]. The effects of parasympatholytic and sympatheticomimetic nebulization therapy in gradient increase in the left ventricular outflow tract: Do they have the same influence?International Journal of CardiologyVol. 203PreviewWe read with great interest the case report by E. Siniorakis et al. [1]. In this case report, they presented a bronchospastic patient who had a significant gradient increase in the left ventricular outflow tract (LVOT) with symptomatic concurrent significant decrease in blood pressure during nebulization of a mixture of ipratropium and salbutamol. We would like to make some comments about this case report from pathophysiological and clinical aspects. Full-Text PDF