QTc Interval and Mortality in a Population of SARS-2-CoV Infected Patients
2020; Lippincott Williams & Wilkins; Volume: 13; Issue: 11 Linguagem: Inglês
10.1161/circep.120.008890
ISSN1941-3149
AutoresAlessandro Vicentini, Lucrezia Masiello, Sabato D’Amore, Enrico Baldi, Stefano Ghio, Simone Savastano, Antonio Sanzo, Angela Di Matteo, Elena Seminari, Marco Vincenzo Lenti, Matteo Bosio, Barbara Petracci, Laura Frigerio, Anna Sabena, Guido Tavazzi, Luigi Oltrona Visconti, Roberto Rordorf, Massimiliano Gnecchi, Rossana Totaro, Marco Ferlini, Alessandra Greco, Giulia Magrini, Laura Scelsi, Mauro Acquaro, Michela Coccia, Simonluca Digiacomo, Davide Foglia, Francesco Jeva, Claudio Montalto, Martina Moschella, Laura Pezza, Stefano Perlini, C Alfano, Marco Bonzano, Domenica Federica Briganti, Giuseppe Crescenzi, Anna Giulia Falchi, Elena Maggi, Roberta Guarnone, Barbara Katia Guglielmana, Ilaria Martino, Maria Serena Pioli Di Marco, Pietro Pettenazza, Federica Quaglia, Francesco Salinaro, Francesco Speciale, Ilaria Zunino, Giulia Sturniolo, Federico Bracchi, Elena López Lago, Angelo Guido Corsico, Davide Piloni, Giulia Accordino, Cecilia Burattini, Antonio Di Sabatino, Ivan Pellegrino, Simone Soriano, Giovanni Santacroce, Alessandro Parodi, F. Borrelli De Andreis, Raffaele Bruno, Valentina Zuccaro, Francesco Moioli, Marco Vincenzo Lenti, Riccardo Albertini,
Tópico(s)ECG Monitoring and Analysis
ResumoHomeCirculation: Arrhythmia and ElectrophysiologyVol. 13, No. 11QTc Interval and Mortality in a Population of SARS-2-CoV Infected Patients Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBQTc Interval and Mortality in a Population of SARS-2-CoV Infected Patients Alessandro Vicentini, MD Lucrezia Masiello, MD Sabato D'Amore, MD Enrico Baldi, MD Stefano Ghio, MD Simone Savastano, MD Antonio Sanzo, MD Angela Di Matteo, MD Elena Maria Seminari, MD Marco Vincenzo Lenti, MD Matteo Bosio, MD Barbara Petracci, MD Laura Frigerio, MD Anna Sabena, MD Guido Tavazzi, MD, PhD Luigi Oltrona Visconti, MD Roberto RordorfMDon behalf of San Matteo COVID Cardiac Injury Task Force Massimiliano Gnecchi, Rossana Totaro, Marco Ferlini, Alessandra Greco, Giulia Magrini, Laura Scelsi, Mauro Acquaro, Michela Coccia, Simonluca Digiacomo, Davide Foglia, Francesco Jeva, Claudio Montalto, Martina Moschella, Laura Pezza, Stefano Perlini, Claudia Alfano, Marco Bonzano, Federica Briganti, Giuseppe Crescenzi, Anna Giulia Falchi, Elena Maggi, Roberta Guarnone, Barbara Guglielmana, Ilaria Francesca Martino, Maria Serena Pioli Di Marco, Pietro Pettenazza, Federica Quaglia, Francesco Salinaro, Francesco Speciale, Ilaria Zunino, Giulia Sturniolo, Federico Bracchi, Elena Lago, Angelo Corsico, Davide Piloni, Giulia Accordino, Cecilia Burattini, Antonio Di Sabatino, Ivan Pellegrino, Simone Soriano, Giovanni Santacroce, Alessandro Parodi, Federica Borrelli de Andreis, Raffaele Bruno, Valentina Zuccaro, Francesco Moioli, Valentino Dammassi, Riccardo Albertini Alessandro VicentiniAlessandro Vicentini Correspondence to: Alessandro Vicentini, MD, Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experimental and Cardiology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7424-3943 Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Lucrezia MasielloLucrezia Masiello https://orcid.org/0000-0002-9660-6212 Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Department of Molecular Medicine, Cardiology Unit (L.M., S.D., E.B.), University of Pavia, Italy. , Sabato D'AmoreSabato D'Amore https://orcid.org/0000-0003-3351-0894 Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Department of Molecular Medicine, Cardiology Unit (L.M., S.D., E.B.), University of Pavia, Italy. , Enrico BaldiEnrico Baldi https://orcid.org/0000-0002-6360-224X Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Department of Molecular Medicine, Cardiology Unit (L.M., S.D., E.B.), University of Pavia, Italy. , Stefano GhioStefano Ghio https://orcid.org/0000-0002-1858-1152 Division of Cardiology (S.G., S.S., L.O.V.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Simone SavastanoSimone Savastano https://orcid.org/0000-0002-9789-6661 Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Antonio SanzoAntonio Sanzo Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Department of Internal Medicine (A.S.), University of Pavia, Italy. Emergency Department (A.S.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Angela Di MatteoAngela Di Matteo https://orcid.org/0000-0002-2307-1544 Division of Infectious Disease (A.D.M., E.M.S.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Elena Maria SeminariElena Maria Seminari https://orcid.org/0000-0001-5246-928X Division of Infectious Disease (A.D.M., E.M.S.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Marco Vincenzo LentiMarco Vincenzo Lenti https://orcid.org/0000-0002-6654-4911 Department of Internal Medicine (M.V.L.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Matteo BosioMatteo Bosio Division of Respiratory Diseases (M.B.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Barbara PetracciBarbara Petracci Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Laura FrigerioLaura Frigerio Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Anna SabenaAnna Sabena Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Guido TavazziGuido Tavazzi https://orcid.org/0000-0002-9560-5138 Anaesthesia and Intensive Care (G.T.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Unit of Anesthesia and Intensive Care (G.T.), University of Pavia, Italy. , Luigi Oltrona ViscontiLuigi Oltrona Visconti Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology (A.V., L.M., S.D., E.B., A.S., B.P., L.F., R.R.), Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. , Roberto RordorfRoberto Rordorf https://orcid.org/0000-0003-4111-1690 and on behalf of San Matteo COVID Cardiac Injury Task Force Originally published29 Sep 2020https://doi.org/10.1161/CIRCEP.120.008890Circulation: Arrhythmia and Electrophysiology. 2020;13:e008890Recent data have highlighted that QTc interval might be at the upper limits or prolonged1 in patients with coronavirus disease 2019 (COVID-19) also before starting QTc prolonging drugs. The aim of the present study was to investigate the relationship between baseline QTc and mortality.We performed a retrospective analysis of ECGs on 318 patients admitted to Policlinico San Matteo Hospital in Pavia, Italy, between February 22, 2020, and April 24, 2020. Patients were defined as infected by a positive nasopharyngeal swab or by clinical diagnosed infection based on symptoms, radiological, and laboratory tests. QT interval was manually measured from a 12-lead ECG using Bazzett's formula. Last follow-up was performed on May 1, 2020. Data are presented as counts (%) or as median (interquartile range [IQR]). Categorical and continuous variables were compared with the χ2 and Mann-Whitney test, respectively. Logistic regression model was used to identify univariable and multivariable predictors of mortality. Odds ratio (95% CI) are presented. A P value <0.05 was considered statistically significant. The local ethical committee approved the publication of anonymized case series of patients with COVID-19 using data collected for clinical practice and waived the requirement for a specific informed consent. The data that support the present findings are available upon request.Males patients were 213 (67%), the median age was 70 years (IQR, 60–78), 200 (63.3%) with history of cardiovascular disease and 27 (8.5%) of chronic obstructive pulmonary disease, 13 (4.1%) were on antiarrhythmic medication and 106 (33.3%) on β-blockers. In-hospital death occurred in 94 (29.6%). The median off-drugs QTc at admission was 440 ms (IQR, 424–465) in males and 444 ms (IQR, 417–459) in females. We divided patients into 2 groups based on the median QTc: not prolonged QTc group (n=151) and prolonged QTc group (n=167).Overall mortality was higher in prolonged QTc group than in not prolonged QTc group (38.3% versus 19.9%, P<0.001; Figure [A]. Patients in prolonged QTc group were older (73 years, IQR, 63–80 versus 68, IQR, 56–74, P<0.001), more frequently with history of cardiovascular disease (69.9% versus 56%, P=0.01) and presence of AF (15.7% versus 3.4%, P<0.001), with higher serum levels of creatinine (0.93 mg/dL, IQR, 0.74–1.24 versus 0.86, IQR, 0.71–1.10; P=0.046), high-sensitivity troponin I (hs-TnI; 19 ng/L, IQR, 8–48.2 versus 11, IQR, 5–30; P=0.006), and lower potassium (3.97 mEq/L, IQR, 3.6–4.4 versus 4.1, IQR, 3.8–4.48; P=0.03) at hospital admission. The percentage of patients with hs-TnI higher than the upper limit of normal (47 ng/mL) was similar in the 2 groups (25.5% in prolonged QTc group versus 19.2% in not prolonged QTc, P=0.22). However, there was no difference regarding sex, heart rate, PaO2/FiO2, C-reactive protein, and white blood count between the 2 groups. Also, the percentage of patients treated with the combination of azithromycin and hydroxychloroquine was comparable (46.7% versus 43.7%, P=0.59).Download figureDownload PowerPointFigure. Mortality in prolonged versus not prolonged QTc groups.A, QTc at admission ECG and in-hospital mortality rate. B, QTc at admission ECG and in-hospital mortality rate in those in whom more than one ECG was available and mortality rate according to the presence of at least one QTc value ≥500 ms at a control ECG. Control ECG was defined as an ECG performed at least 3 d after the admission one. C, Univariable and multivariable analysis of predictors of in-hospital mortality. CV indicates cardiovascular; hs-TnI, high-sensitivity troponin I; and OR, odds ratio.During hospitalization, ECG was repeated in 147 patients (46.2%): analyzing only patients with more than one ECG available, a significantly higher mortality was confirmed in those with baseline QTc greater than the median value (32.5% versus 17.9%, P=0.04, Figure [B]). The number of patients treated with the combination of azithromycin and hydroxychloroquine in these groups was similar (58.7% versus 52.2%, P=0.43). A QTc value≥500 ms, a known marker of extreme cardiac electrical instability,2 was observed in control ECGs in 20% of the patients in the prolonged QTc group versus 7% in the not prolonged QTc group. Noteworthy, mortality was significantly higher in those with baseline prolonged QTc and further prolongation ≥500 ms at control ECG (56.2% versus 26.6%, P=0.02; Figure [B]). The percentage of patients treated with the combination of azithromycin and hydroxychloroquine was higher, but not statistically different in patients with versus without QTc≥500 ms (75% versus 54.7%, P=0.14). Of more, the percentage of patients treated with any QT prolonging medication was not different between those with a QTc≥ or 70 years, ipokaliemia (<3.5 mEq/L), history of cardiovascular disease and AF (Figure [C]).Our results confirm that QTc interval in patients with COVID-19 is higher than expected in a normal population. One of the possible mechanisms explaining this phenomenon is inflammatory cytokines activation, which can suppress IKr (rapid delayed rectifier channel) in heterologous cells and myocytes resulting in prolonged repolarization.3 Moreover, patients with COVID-19 are more susceptible to pulmonary thromboembolism,4 which is known to be linked to QT prolongation.5Furthermore, prolonged QTc interval was found to be a strong predictor of in-hospital mortality with the highest risk in patients with baseline prolonged QTc and further prolongation with a QTc value ≥500 ms observed during hospitalization.Summarizing, QTc might be one of the elements to be considered in risk stratification of patients with COVID-19. We, therefore, suggest to carefully consider baseline QTc interval and to monitor the QTc value during hospitalization. This appear even more important when considering the use of treatments known to further prolong QTc interval.Nonstandard Abbreviations and AcronymsAFatrial fibrillationCOVID-19coronavirus diseasehs-TnIhigh-sensitivity troponin IIQRinterquartile rangeSources of FundingNone.DisclosuresNone.AppendixInvestigators and co-authors of the San Matteo COVID Cardiac Injury Task Force are as follows:Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology: Alessandro Vicentini, Roberto Rordorf, Enrico Baldi, Massimiliano Gnecchi, Rossana Totaro, Sabato D'Amore, Lucrezia Masiello, Antonio Sanzo, Barbara Petracci, Laura Frigerio; Division of Cardiology: Stefano Ghio, Luigi Oltrona Visconti, Marco Ferlini, Alessandra Greco, Giulia Magrini, Laura Scelsi, Simone Savastano, Mauro Acquaro, Michela Coccia, Simonluca Digiacomo Davide Foglia, Francesco Jeva, Lucrezia Masiello, Claudio Montalto, Martina Moschella, Laura Pezza; Emergency Department: Stefano Perlini, Claudia Alfano, Marco Bonzano, Federica Briganti, Giuseppe Crescenzi, Anna Giulia Falchi, Elena Maggi, Roberta Guarnone, Barbara Guglielmana, Ilaria Francesca Martino, Maria Serena Pioli Di Marco, Pietro Pettenazza, Federica Quaglia, Anna Sabena, Francesco Salinaro, Francesco Speciale, Ilaria Zunino, Giulia Sturniolo, Federico Bracchi, Elena Lago; Division of Respiratory Diseases: Angelo Corsico, Davide Piloni, Giulia Accordino, Cecilia Burattini, Matteo Bosio; Division of Internal Medicine: Antonio Di Sabatino, Marco Vincenzo Lenti, Ivan Pellegrino, Simone Soriano, Giovanni Santacroce, Alessandro Parodi, Federica Borrelli de Andreis; Division of Infectious Disease: Raffaele Bruno, Angela Di Matteo, Elena Maria Seminari, Valentina Zuccaro; Intensive Care Unit: Francesco Moioli, Guido Tavazzi, Valentino Dammassi; Clinical Chemistry Laboratory: Riccardo AlbertiniFootnotes*A list of all San Matteo COVID Cardiac Injury Task Force participants is given in the Appendix.For Sources of Funding and Disclosures, see page 1386.Correspondence to: Alessandro Vicentini, MD, Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experimental and Cardiology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy. Email a.[email protected]pv.itReferences1. Saleh M, Gabriels J, Chang D, Soo Kim B, Mansoor A, Mahmood E, Makker P, Ismail H, Goldner B, Willner J, et al.. Effect of chloroquine, hydroxychloroquine, and azithromycin on the corrected QT interval in patients with SARS-CoV-2 infection.Circ Arrhythm Electrophysiol. 2020; 13:e008662. doi: 10.1161/CIRCEP.120.008662LinkGoogle Scholar2. Gibbs C, Thalamus J, Kristoffersen DT, Svendsen MV, Holla ØL, Heldal K, Haugaa KH, Hysing J. QT prolongation predicts short-term mortality independent of comorbidity.Europace. 2019; 21:1254–1260. doi: 10.1093/europace/euz058CrossrefMedlineGoogle Scholar3. Aromolaran AS, Srivastava U, Alí A, Chahine M, Lazaro D, El-Sherif N, Capecchi PL, Laghi-Pasini F, Lazzerini PE, Boutjdir M. Interleukin-6 inhibition of hERG underlies risk for acquired long QT in cardiac and systemic inflammation.PLoS One. 2018; 13:e0208321. doi: 10.1371/journal.pone.0208321CrossrefMedlineGoogle Scholar4. Llitjos JF, Leclerc M, Chochois C, Monsallier JM, Ramakers M, Auvray M, Merouani K. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.J Thromb Haemost. 2020; 18:1743–1746. doi: 10.1111/jth.14869CrossrefMedlineGoogle Scholar5. Punukollu G, Gowda RM, Khan IA, Wilbur SL, Vasavada BC, Sacchi TJ. QT interval prolongation with global T-wave inversion: a novel ECG finding in acute pulmonary embolism.Ann Noninvasive Electrocardiol. 2004; 9:94–98. doi: 10.1111/j.1542-474x.2004.91528.xCrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails November 2020Vol 13, Issue 11Article InformationMetrics Download: 132 © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.120.008890PMID: 32991202 Originally publishedSeptember 29, 2020 Keywordsatrial fibrillationcoronavirusmortalityelectrocardiographyroponin IPDF download SubjectsArrhythmiasSudden Cardiac DeathElectrocardiology (ECG)Mortality/Survival
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