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Effect of triple combination therapy with lopinavir-ritonavir, azithromycin and hydroxychloroquine on QT interval and arrhythmic risk in hospitalized COVID-19 patients.
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  • Vincenzo Russo,
  • Andreina Carbone,
  • Filiberto Fausto Mottola,
  • Rosa Mocerino,
  • Raffaele Verde,
  • Emilio Attena,
  • Nicoletta Verde,
  • Piepaolo Di Micco,
  • Luigi Nunziata,
  • Francesco Santelli,
  • Gerardo Nigro,
  • Sergio Severino
Vincenzo Russo
Second University of Naples - Monaldi Hospital

Corresponding Author:v.p.russo@libero.it

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Andreina Carbone
University of Campania "Luigi Vanvitelli" – Monaldi Hospital, Naples, Italy.
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Filiberto Fausto Mottola
Ospedale Monaldi
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Rosa Mocerino
Cotugno Hospital, Naples, Italy
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Raffaele Verde
Cotugno Hospital
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Emilio Attena
San Giuliano Hospital
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Nicoletta Verde
Ospedale Monaldi
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Piepaolo Di Micco
Madonna del Buon Consiglio Fatebenefratelli di Napoli Hospital
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Luigi Nunziata
Boscotrecase Hospital
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Francesco Santelli
University of Naples Federico II
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Gerardo Nigro
University of Campania Luigi Vanvitelli
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Sergio Severino
Cotugno Hospital
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Introduction: no data are provided about the effect of triple combination therapy with Lopinavir/Ritonavir (LPN/RTN), hydroxychloroquine (HQ) and azithromycin (AZT) on corrected QT (QTc) interval and arrhythmic risk, in COVID-19 patients. This study aims to describe the incidence of extreme QTc interval prolongation among COVID-19 patients on this experimental treatment and to identify the clinical features associated with extreme QTc prolongation. Materials and methods: data of 87 COVID-19 patients, treated with triple combination including LPN/RTN, HQ and AZT, were analyzed. QT interval was obtained by the tangent method and corrected for heart rate using Bazett’s formula. Extreme QTc interval prolongation was considered an absolute QTc interval ≥ 500 ms or an increase in QTc intervals of 60 milliseconds or greater (ΔQTc ≥ 60 milliseconds) compared with baseline. Results: Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. 20 patients (23%) showed extreme QTc interval prolongation; No clinical, electrocardiographic or pharmacological characteristics have been associated to extreme QTc prolongation, except the history of ischemic stroke (P= 0,007). One torsade de pointes (TdP) in patient with QTc extreme prolongation (QTc: 560 ms) after 5 days of therapy was recorded. Conclusions: We observed a high incidence of extreme QTc interval prolongation among COVID-19 patients on triple combination therapy. The incidence of malignant arrhythmias seems to be low, a careful electrocardiographic monitoring would be advisable.