Medicines and QT Prolongation

Abstract As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

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Changes of QT interval in the acute phase after pulmonary vein isolation for paroxysmal atrial fibrillation

European Heart Journal ◽

10.1093/ehjci/ehaa946.0414 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Chikata ◽

T Kato ◽

K Ududa ◽

S Fujita ◽

K Otowa ◽

...

Keyword(s):

Atrial Fibrillation ◽

Pulmonary Vein ◽

Female Patient ◽

Pulmonary Vein Isolation ◽

Acute Phase ◽

Paroxysmal Atrial Fibrillation ◽

Qt Interval ◽

Qt Prolongation ◽

Qtc Interval ◽

The Impact

Abstract Introduction Pulmonary vein isolation (PVI) affects ganglionated plexi (GP) around the atrium, leading to a modification of the intrinsic cardiac autonomic system (ANS). In animal models, GP ablation has a potential risk of QT prolongation and ventricular arrhythmias. However, the impact of PVI on QT intervals in humans remains unclear. Purpose This study aims to evaluate the Impact of PVI on QT interval in patients with paroxysmal atrial fibrillation. Methods We analyzed consecutive 117 PAF patients for their first PVI procedures. 12-lead ECG was evaluated at baseline, 4 hr, day 1, 1 month, and 3 months after ablation. Only patients with sinus rhythm on 12-lead ECG at each evaluation point without antiarrhythmic drugs were included. Results Heart rate significantly increased at 4 hr, day 1, and 1 month. Raw QT interval prolonged at 4 hr (417.1±41.6 ms, P<0.001) but shortened at day 1 (376.4±34.1 ms, P<0.001), 1 month (382.2±31.5 ms, P<0.001), and 3 months (385.1±32.8 ms, P<0.001) compared to baseline (391.6±31.4 ms). Bazett- and Fridericia- corrected QTc intervals significantly prolonged at 4hr (Bazett: 430.8±27.9 ms, P<0.001; Fridericia: 425.8±27.4 ms, P<0.001), day1 (Bazett: 434.8±22.3 ms, P<0.001; Fridericia: 414.1±23.7 ms, P<0.001), 1M (Bazett: 434.8±22.3 ms, P<0.001; Fridericia: 408.2±21.0 ms, P<0.05), and 3M (Bazett: 420.1±21.8 ms, P<0.001; Fridericia: 407.8±21.1 ms, P<0.05) compared to baseline (Bazett: 404.9±25.2 ms; Fridericia: 400.0±22.6 ms). On the other hand, Framingham- and Hodges- corrected QTc interval significantly prolonged only at 4hr (Framingham: 424.1±26.6 ms, P<0.001; Hodges: 426.8±28.4 ms, P<0.001) and at day1 (Framingham: 412.3±29.3 ms, P<0.01; Hodges: 410.6±40.2 ms, P<0.05) compared to baseline (Framingham: 399.2±22.7 ms; Hodges: 400.7±22.8 ms). At 4 hr after ablation, raw QT and QTc of all formulas significantly prolonged than baseline. Raw QT and QTc prolongation at 4hr after ablation were more frequently observed in female patients. Multiple regression analysis revealed that female patient is a significant predictor of raw QT and QTc interval prolongation of all formulas 4hr after PVI. Conclusions Raw QT and QTc prolonged after PVI, especially in the acute phase. Female patient is a risk factor for QT prolongation in the acute phase after PVI. Funding Acknowledgement Type of funding source: None

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1 COVID-19 and QTc: is hydroxychloroquine worth the risk? A review of QT prolongation in hospitalised COVID-19 patients treated with hydroxychloroquine and azithromycin

10.1136/heartjnl-2020-ics.1 ◽

2020 ◽

Author(s):

A Pollock ◽

R Kumar ◽

P Devitt ◽

B Kent ◽

C Daly

Keyword(s):

Qt Prolongation

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QT prolongation associated with hydroxychloroquine and protease inhibitors in COVID‐19

Journal of Clinical Pharmacy and Therapeutics ◽

10.1111/jcpt.13356 ◽

2021 ◽

Author(s):

Hui Moon Koh ◽

Pei Feng Chong ◽

Ju Nee Tan ◽

Suresh Kumar Chidambaram ◽

Hiu Jian Chua

Keyword(s):

Protease Inhibitors ◽

Qt Prolongation

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An explainable algorithm for detecting drug-induced QT-prolongation at risk of torsades de pointes (TdP) regardless of heart rate and T-wave morphology

Computers in Biology and Medicine ◽

10.1016/j.compbiomed.2021.104281 ◽

2021 ◽

Vol 131 ◽

pp. 104281

Author(s):

Alaa Alahmadi ◽

Alan Davies ◽

Jennifer Royle ◽

Leanna Goodwin ◽

Katharine Cresswell ◽

...

Keyword(s):

At Risk ◽

Heart Rate ◽

Torsades De Pointes ◽

Qt Prolongation ◽

Drug Induced ◽

T Wave ◽

Wave Morphology

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QT Prolongation in Dialysis Patients: An Epidemiological Study with a Focus on Malnutrition

Blood Purification ◽

10.1159/000512961 ◽

2021 ◽

pp. 1-8

Author(s):

Masanori Shibata ◽

Isao Ito ◽

Hisae Tawada ◽

Shinkichi Taniguchi

Keyword(s):

Risk Index ◽

Bioelectrical Impedance ◽

Impedance Analysis ◽

Serum Levels ◽

Qt Prolongation ◽

Fat Free Mass ◽

Nutritional Risk ◽

Diabetic Patients ◽

Qtc Interval ◽

Nutritional Risk Index

Background/Aims: QT prolongation is a known risk factor for ventricular fibrillation and ventricular tachycardia. Therefore, more refined management is necessary to reduce sudden cardiac death secondary to such arrhythmias. Methods: Electrocardiographic findings were reviewed in 224 patients, and the associations of QT prolongation with various clinical parameters were examined, including the nutritional state. Correlations were also examined between QT prolongation and body composition measurements determined by multifrequency bioelectrical impedance analysis. Results: Prolongation of the corrected QT (QTc) interval over 0.44 s was seen in 140 patients (62.5%). QT prolongation was independent of age and dialysis therapy duration and was more frequent in diabetics (70.1%) than in nondiabetics (54.2%, p = 0.014) and more frequent in women (78.8%) than in men (53.5%, p < 0.001). Serum levels of albumin (p < 0.001) and Cr (p < 0.001) and the Geriatric Nutritional Risk Index (GNRI, p < 0.001) were negatively correlated with QTc interval; no significant correlation was noted with total protein, urea nitrogen, or uric acid. Negative correlations with QTc interval were found for BMI(p < 0.01), percent total body water (%TBW; p < 0.05), and percent intracellular water (%ICW; p < 0.01) but not with the percent extracellular water/TBW ratio or edema ratio. The longer the QTc interval, the lower the fat-free mass (FFM; p < 0.01) and muscle mass (MM; p < 0.01), but there was no significant correlation with percent fat. Conclusion: These results suggest that QT prolongation is a common complication and is more frequent in women and diabetic patients. The decreases in serum albumin and Cr levels, GNRI, BMI, %TBW, %ICW, FFM, and MM together coincided with malnutrition and thus suggest a close relationship of QT prolongation with malnutrition. Management of QT prolongation may be achieved better in the future by understanding these biochemical and biophysical changes, particularly those regarding malnutrition.

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