A Study to Compare the Prolongation of the Corrected QT Interval of Rheumatoid Arthritis Patients on Hydroxychloroquine

Background: For rheumatoid arthritis (RA) patients, hydroxychloroquine (HCQ) is a staple treatment. Concerns about its cardiovascular safety have been raised after reports of its use and fatal arrhythmias in individuals with coronavirus illness 19. Aims and objectives: To examine the relationship between HCQ use and corrected QT (QTc) length in RA patients. Material(s) and Method(s): Hundred subjects (age >= 18 years) were studied after dividing them in to Cases (n=50;patients with RA taking HCQ) and Control (n=50;patients without RA not taking HCQ) at the Department of General Medicine of a tertiary care center in Madhya Pradesh. Patient characteristics and laboratory measures, including rheumatoid factor hemoglobin, white blood cells count, platelets, erythrocyte sedimentation rate (ESR), random blood sugar, urea, Creatinine, SGOT, SGPT, serum electrolytes, calcium, and magnesium level, were assessed. QTc length was obtained with the help of 12-lead ECG. Result(s): Incidence of QTc prolongation in patients with RA was 11%. Odds for prolonged QTc interval for patients with age >50 years was 3.500 (95% CI = 0.865-14.155), serum calcium <8 was 2.400 (95% CI = 0.540-10.666), and ESR >20 was 0.756 (95% CI = 0.640-0.892). A significant positive correlation was obtained between prolonged QTc with age (r=0.283;p=0.046). Conclusion(s): There is a significant increase in risk of QTc prolongation with the use of HCQ in patients with RA. Copyright © 2022, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

A case report on the association between QTc prolongation and remdesivir therapy in a critically ill patient.

Remdesivir is a direct-acting inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase that is used to treat severe COVID-19 infections. We report a patient with severe COVID-19 pneumonia who experienced palpitations and syncope two days after starting remdesivir therapy. The QTc interval was prolonged on the Electrocardiogram (ECG) without any significant electrolyte abnormalities or concomitant use of medications with QTc prolongation. Although the cardiac side effects of remdesivir therapy have been well documented, the link between remdesivir therapy and QTc interval prolongation in patients with severe COVID-19 has only been observed in a few cases. Because this arrhythmia has the potential to result in sudden cardiac death, practitioners should be aware of the QTc interval prolongation associated with remdesivir therapy.

Cardiotoxicity of azithromycin in COVID-19: an overall proportion meta-analysis.

INTRODUCTION: To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. MATERIAL AND METHODS: We searched PubMed, the Cochrane Library and Web of Science databases from inception to 18 January 2021, as well as the medRχiv preprint database from 1 August 2020 to 18 January 2021, for studies exploring the cardiotoxicity effects of azithromycin, with or without concomitant use of hydroxychloroquine, in the context of Covid19. We performed a random effects single-arm meta-analysis of studies to calculate pooled proportion estimates for pro-arrhythmic effects. Meta-regression analyses were conducted to explain between-study heterogeneity. RESULTS: Thirty-four studies with a total of 3088 patients were included. Among 12 studies, the incidence of > 60ms QTc prolongation from baseline was 13% (95% CI 9%-18%, I² = 73%), whereas, among 28 studies, the incidence of QTc ≥ 500 ms at follow-up was 8% (95% CI 6%-11%, I² = 78%). Still, the discontinuation rate due to QTc prolongation was only 3% (95% CI 2%-5%, I² = 55%). The absolute risk of Torsade de pointes and ventricular tachycardia was 0.2% and 0.8%, respectively. Increased age, male sex, presence of hypertension or diabetes mellitus, use of QTc prolonging medication, prolonged baseline QTc interval and indicators of disease severity such as death explained between-study heterogeneity. CONCLUSIONS: Azithromycin, with or without hydroxychloroquine, leads to a significant risk for critical QTc prolongation in patients with Covid19. Due to its cardiotoxicity effects and its unproven efficacy in Covid19, azithromycin use should be limited to cases of bacterial co-infection.

QTc Interval Prolongation and Life-Threatening Arrhythmias During Hospitalization in Patients With Coronavirus Disease 2019 (COVID-19): Results From a Multicenter Prospective Registry.

BACKGROUND: Prolonged QTc intervals and life-threatening arrhythmias (LTA) are potential drug-induced complications previously reported with antimalarials, antivirals, and antibiotics. Our objective was to evaluate the prevalence and predictors of QTc interval prolongation and incidences of LTA during hospitalization for coronavirus disease 2019 (COVID-19) among patients with normal admission QTc. METHODS: We enrolled 110 consecutive patients in a multicenter international registry. A 12-lead electrocardiograph was performed at admission, after 7, and at 14 days; QTc values were analyzed. RESULTS: After 7 days, 15 (14%) patients developed a prolonged QTc (pQTc; mean QTc increase 66 ± 20 msec; +16%; P < .001); these patients were older and had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, and lower platelet counts. The QTc increase was inversely proportional to the baseline QTc level and leukocyte count and directly proportional to the basal heart rate (P < .01).We conducted a multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate, and dual antiviral therapy; age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; P < .05), basal heart rate (OR, 1.07; 95% CI, 1.02-1.13; P < .01), and dual antiviral therapy (OR, 12.46; 95% CI, 2.09-74.20; P < .1) were independent predictors of QT prolongation.The incidence rate of LTA during hospitalization was 3.6%. There was 1 patient who experienced cardiac arrest and 3 with nonsustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of the mortality rate. CONCLUSIONS: After 7 days of hospitalization, 14% of patients with COVID-19 developed pQTc; age, basal heart rate, and dual antiviral therapy were found to be independent predictors of pQTc. Life-threatening arrhythmias have an incidence rate of 3.6%, and were associated with a poor outcome.

Effects of hydroxychloroquine and its metabolites in patients with connective tissue diseases.

Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.

Potential Cardiotoxic Effects of Remdesivir on Cardiovascular System: A Literature Review.

Corona disease 2019 (COVID-19) pandemic continues to spread around the world with no efficacious treatment. Intravenous remdesivir is the only authorized drug for treatment of COVID-19 disease under an Emergency Use Authorization. Remdesivir is a 1'-cyano-substituted adenosine nucleotide prodrug which inhibits viral RNA synthesis. This metabolite is an adenosine analog but with a significantly longer half-life than adenosine. Adenosine is a powerful vasodilator that can cause profound hypotension which is followed by the compensatory release of catecholamines. It can also shorten atrial action potential and refractoriness and lead to atrial fibrillation (AF). These effects may also occur in ventricular cells and predispose patients to ventricular fibrillation. Remdesivir can also induce significant cytotoxic effects in cardiomyocytes that is considerably worse than chloroquine cardiotoxic effects. Remdesivir-induced cardiotoxicity is due to its binding to human mitochondrial RNA polymerase. On the other hand, remdesivir can increase field potential duration with decreased Na+ peak amplitudes and spontaneous beating rates in a dose-dependent manner that might induce prolonged QT interval and torsade de point. There are some reports of sinus bradycardia, hypotension, T-wave abnormalities, AF, and a prolonged QT interval and few cases of cardiac arrest and complete heat block following remdesivir infusion. It seems remdesivir have some cardiotoxic and proarrhythmic effects that are especially more pronounced in patients with previous cardiovascular diseases. The current safety profile of remdesivir is still not completely known and further prospective clinical trials are needed to assess its safety profile and potential adverse cardiovascular effects.

Corrected QT Interval Prolongation, Elevated Troponin, and Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has risen to the level of a global pandemic. Growing evidence has proven the cardiac involvement in SARS-CoV-2 infection. This study aims to evaluate the ability of cardiovascular complications determined by elevated troponin and electrocardiogram findings (e.g., corrected QT interval (QTc)) in predicting the severity of SARS-CoV-2 infection among hospitalized patients. METHODS: This is a retrospective review of medical records of 800 patients, admitted to Richmond University Medical Center in Staten Island, NY, and tested positive for SARS-CoV-2 between March 1, 2020 and July 31, 2020. A total of 339 patients met the study inclusion and exclusion criteria and were included in statistical analysis. RESULTS: Elevated serum troponin levels on admission statistically correlated with mortality in SARS-CoV-2 patients. Prolonged QTc was shown to have an independent statistically significant association with mortality among patients hospitalized with SARS-CoV-2. CONCLUSIONS: Growing concern for cardiovascular sequelae of coronavirus disease 2019 (COVID-19) has prompted many researchers to investigate the role of cardiovascular complications in mortality due to SARS-CoV-2. Obtaining a simple electrocardiogram for hospitalized patients with COVID-19 could provide an independent prognostic tool and prompt more coordinated treatment strategies to prevent mortality among patients hospitalized with COVID-19.

Effect of Hydroxychloroquine on QTc in Patients Diagnosed with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Hydroxychloroquine or chloroquine with or without the concomitant use of azithromycin have been widely used to treat patients with SARS-CoV-2 infection, based on early in vitro studies, despite their potential to prolong the QTc interval of patients. OBJECTIVE: This is a systematic review and metanalysis designed to assess the effect of hydroxychloroquine with or without the addition of azithromycin on the QTc of hospitalized patients with COVID-19. MATERIALS AND METHODS: PubMed, Scopus, Cochrane and MedRxiv databases were reviewed. A random effect model meta-analysis was used, and I-square was used to assess the heterogeneity. The prespecified endpoints were ΔQTc, QTc prolongation > 500 ms and ΔQTc > 60 ms. RESULTS: A total of 18 studies and 7179 patients met the inclusion criteria and were included in this systematic review and meta-analysis. The use of hydroxychloroquine with or without the addition of azithromycin was associated with increased QTc when used as part of the management of patients with SARS-CoV-2 infection. The combination therapy with hydroxychloroquine plus azithromycin was also associated with statistically significant increases in QTc. Moreover, the use of hydroxychloroquine alone, azithromycin alone, or the combination of the two was associated with increased numbers of patients that developed QTc prolongation > 500 ms. CONCLUSION: This systematic review and metanalysis revealed that the use of hydroxychloroquine alone or in conjunction with azithromycin was linked to an increase in the QTc interval of hospitalized patients with SARS-CoV-2 infection that received these agents.

QT prolongation associated with hydroxychloroquine and protease inhibitors in COVID-19.

WHAT IS KNOWN AND OBJECTIVE: Hydroxychloroquine and protease inhibitors were widely used as off-label treatment options for COVID-19 but the safety data of these drugs among the COVID-19 population are largely lacking. Drug-induced QTc prolongation is a known adverse reaction of hydroxychloroquine, especially during chronic treatment. However, when administered concurrently with potential pro-arrhythmic drugs such as protease inhibitors, the risk of QTc prolongation imposed on these patients is not known. We aim to investigate the incidence of QTc prolongation events and potential factors associated with its occurrence in COVID-19 population. METHODS: We included 446 SARS-CoV-2 RT-PCR-positive patients taking at least one treatment drug for COVID-19 within a period of one month (March-April 2020). In addition to COVID-19-related treatment (HCQ/PI), concomitant drugs with risks of QTc prolongation were considered. We defined QTc prolongation as QTc interval of ≥470 ms in postpubertal males, and ≥480 ms in postpubertal females. RESULTS AND DISCUSSION: QTc prolongation events occurred in 28/446 (6.3%) patients with an incidence rate of 1 case per 100 person-days. A total of 26/28 (93%) patients who had prolonged QTc intervals received at least two pro-QT drugs. Multivariate analysis showed that HCQ and PI combination therapy had five times higher odds of QTc prolongation as compared to HCQ-only therapy after controlling for age, cardiovascular disease, SIRS and the use of concurrent QTc-prolonging agents besides HCQ and/or PI (OR 5.2; 95% CI, 1.11-24.49; p = 0.036). Independent of drug therapy, presence of SIRS resulted in four times higher odds of QTc prolongation (OR 4.3; 95% CI, 1.66-11.06; p = 0.003). In HCQ-PI combination group, having concomitant pro-QT drugs led to four times higher odds of QTc prolongation (OR 3.8; 95% CI, 1.53-9.73; p = 0.004). Four patients who had prolonged QTc intervals died but none were cardiac-related deaths. WHAT IS NEW AND CONCLUSION: In our cohort, hydroxychloroquine monotherapy had low potential to increase QTc intervals. However, when given concurrently with protease inhibitors which have possible or conditional risk, the odds of QTc prolongation increased fivefold. Interestingly, independent of drug therapy, the presence of systemic inflammatory response syndrome (SIRS) resulted in four times higher odds of QTc prolongation, leading to the postulation that some QTc events seen in COVID-19 patients may be due to the disease itself. ECG monitoring should be continued for at least a week from the initiation of treatment.

Progress in the risk assessment of hydroxychloroquine in frail elderly people.

Hydroxychloroquine (HCQ) is an antimalarial drug also known to have anti-inflammatory and antiviral effects. The antiviral action of HCQ has been a point of interest for many researchers because of its mechanism of action and the potential use it could have during the current COVID-19 pandemic. However, HCQ can cause QT interval prolongation. The current therapies used in COVID-19 are changing as the pandemic develops. The aim of this article is to promote a validated risk score for QT prolongation in multidimensional assessment of COVID-19 patients, especially in elderly and polypathological patients.

Hydroxychloroquine for the treatment and prophylaxis of COVID-19: The journey so far and the road ahead.

As mortality and morbidity from novel coronavirus disease (COVID-19) continue to mount worldwide, the scientific community as well as public health systems are under immense pressure to contain the pandemic as well as to develop effective medical countermeasures. Meanwhile, desperation has driven prescribers, researchers as well as administrators to recommend and try therapies supported by little or no reliable evidence. Recently, hydroxychloroquine-sulfate (HCQS) has got significant media and political attention for the treatment as well as prophylaxis of COVID-19 despite the lack of convincing and unequivocal data supporting its efficacy and safety in these patients. This has unfortunately, yet foreseeably led to several controversies and confusion among the medical fraternity, the patient community as well as the general public. Based on the available studies, many with high risk of bias, relatively small sample sizes, and abbreviated follow-ups, HCQS is unlikely to be of dramatic benefit in COVID-19 patients and yet has the potential to cause harm, particularly when used in combination with azithromycin or other medications in high risk individuals with comorbidities. Although definitive data from larger well-controlled randomized trials will be forthcoming in the future, and we may be able to identify specific patient subpopulations likely to benefit from hydroxychloroquine, till that time it will be prudent to prescribe it within investigational trial settings with close safety monitoring. Here we review the current evidence and developments related to the use of HCQS in COVID-19 patients and highlight the importance of risk-benefit assessment and rational use of HCQS during this devastating pandemic.

Electrical storm in a patient with COVID-19 treated with hydroxychloroquine: A case report.

Hydroxychloroquine (HCQ) is a widely used drug to treat patients with coronavirus disease 19 (COVID-19). Although evidence of its efficacy and safety remains limited and controversial, both cardiac and non-cardiac adverse events are known to be associated with its use. To our knowledge, electrical storm in patients with COVID-19, or in any case treated with HCQ, has not been reported. We report the case of a 78-year-old male with an implantable cardiac resynchronization defibrillator (CRT-D) and a non-severe form of COVID-19. After a few days of home therapy with HCQ, an electrical storm was revealed that was associated with an increase in QTc. Following admission to the intensive care unit, HCQ was discontinued and progressive reduction of the QTc with electrical stabilization was observed. This clinical case highlights the potential risk of arrythmia associated with the use of HCQ and stresses the need for close electrocardiographic monitoring, especially in patients with established heart disease.

HCQ prophylaxis in COVID-19 did not show any QTc prolongation in Healthcare workers.

BACKGROUND: HCQ is a commonly recommended drug for the prophylaxis of COVID-19. One of its rare side-effect includes QTc prolongation. METHODS: This was a prospective, cross sectional and observational study conducted on Hydroxychloroquine (HCQ) among Healthcare Workers (HCWs) at Max Super Speciality Hospital, Saket, New Delhi, India. A 3-lead ECG (only limb leads, it does not require chest leads) was performed. The QTc cut offs were pre decided, QTC < 470 ms for males and <480 ms for females was considered within the normal limits and anything above this was regarded as QTc prolongation. RESULTS: There were 274 HCWs enrolled into the study, including 175 males and 99 females. Majority of the HCWs were young and had a mean age of 32.19 ± 9.29 years. Out of these, 218 were taking HCQ as per the Indian Council of Medical Research (ICMR) guidelines. The median cumulative dose being taken was 1600 mg and the median QTc of these participants was 390 ms in males and 391.5 ms in females. Subsequently, 33 participants were followed-up and found to have a median QTc of 389 ms and a cumulative dose of HCQ as 2000 mg. CONCLUSION: In conclusion, ours is a first study in the middle of the pandemic which showed that HCQ prophylaxis in young HCWs without comorbidities did not show any QTc prolongation.

Ventricular repolarization indexes in patients treated with hydroxychloroquine - azithromycin combination for COVID-19.

BACKGROUND: Combination of hydroxychloroquine and azithromycin for the treatment of coronavirus disease 2019 (COVID-19) carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE:  To characterize the ventricular repolarization indexes which are associated with malignant ventricular arrhythmias in patients treated with hydroxychloroquine and concomitant azithromycin for COVID-19. METHOD: A total of 81 patients who had hydroxychloroquine and azithromycin combination therapy because of possible or  reverse-transcription polymertase chain reaction (RT-PCR) confirmed diagnosis of COVID-19 were included in the study. Baseline and control electrocardiograms (before and after treatment) were analyzed retrospectively. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios, which are ventricular repolarization indexes, were calculated. RESULTS: While there was no significant increase in QTc interval in patients receiving combination therapy, there was a significant increase in ventricular repolarization indexes. CONCLUSION: The increase in ventricular replarization indexes is associated with the risk of arrhythmia. In patients using QTc prolonging medication for COVID-19 treatment, QTc monitoring alone may not be sufficient to follow-up for arrhythmia. Even if there is no prolongation in QTc, an increase in ventricular repolarization indexes may be seen (Tab. 5, Ref. 37).

Cardiac Adverse Events With Remdesivir in COVID-19 Infection.

Since December 2019, coronavirus has gradually progressed to a pandemic with no efficacious treatment. Remdesivir is an antiviral medication and inhibitor of viral RNA dependent RNA polymerase with inhibitory action against SARS-CoV virus. Two patients diagnosed with coronavirus infection with worsening respiratory status were initiated with multimodality therapy with antibiotics, steroids and remdesivir. After initiation of remdesivir, the patients' developed bradycardia, with one of the two also showing signs of worsening QT interval. This reverted upon stopping remdesvir therapy. The prevalence of bradycardia with prolonged QT interval is not well-known yet with this medication.

Effect of Triple Combination Therapy With Lopinavir-Ritonavir, Azithromycin, and Hydroxychloroquine on QT Interval and Arrhythmic Risk in Hospitalized COVID-19 Patients.

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 ms or greater (ΔQTc ≥ 60 ms) compared with baseline. RESULTS: Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. Twenty 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. Since the incidence of malignant arrhythmias seems to be not negligible, a careful electrocardiographic monitoring would be advisable.

Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Among many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin. AIMS: This meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19. METHODS: A comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio. RESULTS: A total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59-17.82%, I2 - 92%), 10.22% (6.01-16.85%, I2 - 79%), and 0.72% (0.34-1.51, I2 - 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22-15.52, I2 - 59%) and 8.61% (4.52-15.79, I2 - 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77-1.93, I2 - 0%) & 1.51 (0.79-2.87, I2 - 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition). CONCLUSION: The use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.

Incomplete Trifascicular Block and Mobitz Type II Atrioventricular Block in COVID-19.

A 74-year-old female with a history of diabetes presented with chest pain and shortness of breath for two days. She was hypoxic to an oxygen saturation of 60% in the emergency department, requiring bilevel positive airway pressure (BiPAP) to maintain saturations. Chest X-ray demonstrated bilateral hazy opacities suspicious for viral pneumonia. Coronavirus disease 2019 (COVID-19) was confirmed. Right bundle branch block (RBBB) with left anterior fascicular block was noted on admission electrocardiogram (ECG). Cardiac enzymes and brain natriuretic peptide levels were within normal limits. After noting frequent pauses on telemetry, a repeat ECG was performed that demonstrated RBBB with left posterior fascicular block as well as second-degree atrioventricular block (Mobitz type II). Transcutaneous pacing pads were placed, and atropine was placed at the bedside. Cardiac enzymes remained negative. Interleukin-6 levels were elevated at 159 pg/mL. Hydroxychloroquine was deferred due to the patient's arrhythmia and prolonged QTc. Tocilizumab was deferred due to the patient's age. The patient's oxygen requirements and mental status continued to worsen. She continued to desaturate despite maximal BiPAP therapy and eventually died. Cardiac involvement in COVID-19, whether caused primarily by the virus, secondary to its clinical sequelae, or even due to its treatment, cannot be ignored. Further high-quality research is needed to clarify the cardiac pathophysiology. Thorough cardiac exams with electrocardiographic correlation should be performed on all patients with COVID-19. Clinicians should not hesitate to consult cardiovascular services in the event of abnormality.

Palliative and Supportive Care Prescribing Considerations Around QT Prolongation Risk in the Context of COVID-19 (Coronavirus Disease 2019) Management.

COVID-19 brings with it unprecedented challenges in clinical management. An important component of care is the provision of safe and effective symptom control. Given the emerging literature reporting on the risk of QT prolongation and arrhythmias associated with COVID-19 disease and experimental therapies, we highlight some considerations for the prescribing of palliative care medications in this context. Based on the experience gained from palliative care referrals at our institution prior to and during the COVID-19 pandemic, and in collaboration with our clinical pharmacology colleagues, we outline some general prescribing principles which may assist with weighing the risks and benefits of prescribing symptomatic medications in and beyond the current pandemic.