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2021, vol. 18, br. 2, str. 63-73
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QTc interval i ishod lečenja bolesnika sa COVID-19
The QTc interval and treatment outcome of inpatients with COVID-19
Jovanović Jovan B.a, Janković Slobodan M.b  , Zdravković Natašac , Davidović Gorana , Veselinović Mirjanac, Čanović Petard , Zarić Miland , Sazdanović Majae , Sazdanović Predragf, Pantić Katarinag, Čekerevac Ivang , Folić Marko M.h , Zečević-Ružić Dejanai, Baskić Dejanj , Đorđević Natašad , Milovanović Dragan R.b
aUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za internu medicinu + Klinički centar Kragujevac, Klinika za kardiologiju bUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za farmakologiju i toksikologiju + Klinički centar Kragujevac, Služba za kliničku farmakologiju cUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za internu medicinu + Klinički centar Kragujevac, Klinika za internu medicinu dUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za farmakologiju i toksikologiju eUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Patohistološka katedra fUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za anatomiju i sudsku medicinu + Ministry of Health of the Republic of Serbia, Belgrade gUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za internu medicinu + Klinički centar Kragujevac, Klinika za pulmologiju hKlinički centar Kragujevac, Služba za kliničku farmakologiju + Univerzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za farmakologiju i toksikologiju iKlinički centar Kragujevac, Klinika za kardiologiju + Klinički centar Kragujevac, Služba za kliničku farmakologiju jUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za mikrobiologiju i imunologiju + Public Health Institute, Kragujevac
e-adresa: jovanovmejl1@gmail.com
Projekat: Farmakološka analiza efekata biološki aktivnih supstanci na izolovane glatke mišiće gastrointestinalnog i urogenitalnog trakta čoveka (MPNTR - 175007)
Sažetak
Cilj. Nakon početka pandemije COVID-19 izazvane virusom SARS-CoV-2, pao je ogroman pritisak na ceo zdravstveni sistem. Pošto za ovu bolest ne postoji adekvatan lek, pribeglo se nelicenciranoj upotrebi nekoliko lekova (azitromicin, hlorokin, hidroksihlorokin i dr.). Cilj ove studije je bio da se analizira dinamika QTc intervala i njegov odnos sa drugim faktorima koji mogu uticati na ishod kod pacijenata sa COVID-19. Metode. Studija je imala opservacioni dizajn slučaj-kontrola sa retrospektivnim prikupljanjem podataka iz medicinske dokumentacije odraslih pacijenata, sa RT-PCR potvrđenim COVID-19. Slučajevi (n=30) su bili bolesnici sa smrtnim ishodom, a kontrole (n=169) su bili preživeli. QTc interval je izračunat pri prijemu, tokom i nakon inicijalne primene lekova sa pretpostavljenom aktivnošću protiv SARS-CoV-2, uglavnom antimalarika. Primarne nezavisne varijable i varijable ishoda bile su produženje QTc intervala odnosno mortalitet od svih uzroka. Rezultati. Ispitivana populacija je uključivala 120 muškaraca (60,3%), prosečna starost pacijenata bila je 57,3+-15,8 godina (+-SD). Najčešća komorbidna oboljenja bila su hipertenzija (98 pacijenata), postojeće aritmije (32) i dijabetes melitus (29). Najčešće propisivani lekovi koji su mogli da produže QTc interval bili su azitromicin (69,8% pacijenata), hlorokin (50,3%) i hidroksihlorokin (42,7%). Ukupno 131 pacijent (65,8%) imao je povećanje QTc intervala >60 ms u odnosu na početnu liniju, od kojih je 5 imalo produženje QTc intervala >500 ms (2,5%). De novo ventrikularne tahiaritmije su registrovane kod 14 pacijenata (7%) a od njih, umrlo je 13 (92,8%). Prethodno postojeće aritmije (odnos šanse 9,30, 95% interval poverenja 2,91-29,73, p<0,001) i furosemid (8,94, 3,27-24,41, p<0,001) su nezavisno povezani sa mortalitetom ali ne i produženje QTc intervala (1,02, 0,22-4,67, p=0,974). Stopa smrtnosti iznosila je 15,1%, pošto je 30 pacijenata umrlo tokom hospitalizacije. Zaključak: Klinički značaj produženja QTc intervala izazvanog lekovima kod hospitalizovanih pacijenata sa COVID-19 treba prvenstveno razmotriti u kontekstu drugih rizika, posebno starije životne dobi, postojećih kardiovaskularnih poremećaja i velikih poremećaja elektrolita.
Abstract
Objective. After the beginning of the COVID-19 pandemic caused by the SARS-CoV -2 virus, enormous pressure fell on the entire health system. Since there is no adequate cure for this disease, "off-label" use of several drugs (azithromycin, chloroquine, hydroxychloroquine, etc.) was resorted to. The aim of this study was to analyse QTc interval dynamics and its relationship with other factors which could influence outcome in patients with COVID-19. Methods. Study has observational, case-control design with retrospective data collection from medical files of adult patients, with RT-PCR confirmed COVID-19. The cases (n=30) were subjects with fatal outcome and the controls (n=169) were the survivors. The QTc interval was calculated on admission, during and after initial drug treatments with presumed activity against SARS-CoV-2, mostly antimalarials. Primary independent and outcome variables were QTc interval prolongation and all-cause mortality, respectively. Results. Study population included 120 males (60.3%), the mean patients age was 57.3+-15.8 years (+-SD). The most common comorbid illnesses were hypertension (98 patients), pre-existing arrhythmias (32) and diabetes mellitus (29). The most frequently prescribed QTc prolonging drugs were azithromycin (69.8% of patients), chloroquine (50.3%) and hydroxychloroquine (42.7%). Total of 131 patients (65.8%) had QTc interval increase >60 ms from baseline, of whom 5 had QTc prolongation >500 ms (2.5%). De novo ventricular tachyarrhythmias were registered at 14 patients (7%) and 13 (92.8%) of them died. Pre-existing arrhythmias (odds ratio 9.30, 95% confidence interval 2.91-29.73, p<0.001) and furosemide (8.94, 3.27-24.41, p<0.001) were independently associated with mortality but QTc prolongation (>480 ms) did not (1.02, 0.22-4.67, p=0.974). Case fatality rate was 15.1%, as 30 patients died during hospitalization. Conclusion. Clinical importance of drug-induced QTc interval prolongation of hospitalized patients with COVID-19 should be considered primarily within the context of other risks, particularly older age, pre-existing cardiovascular disorders and major electrolyte disturbances.
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