Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
Add filters

Document Type
Year range
1.
Pan Afr Med J ; 40: 67, 2021.
Article in English | MEDLINE | ID: covidwho-1497893

ABSTRACT

Adverse consequences of the coronavirus disease 2019 (COVID-19) vaccination which have been reported in scientific papers are varied. One possible but rare consequence is myocarditis, which may have a diversity of clinical manifestations. We report a case of a 70-year-old man who presented to the hospital for some syncope, 3 days after his first COVID-19 AstraZeneca Vaccination. Initial electrocardiogram (ECG) showed a long QT interval (QTc = 600 milliseconds). Laboratory tests revealed elevated troponin and lack of evidence of viral infection. Further investigations revealed the vaccine-induced myocarditis and arrhythmias linked to it. Within one week of magnesium treatment, the QT interval was completely corrected, and the patient discharged with no typical syncope attacks. This case like the previous reported one confirms that myocarditis is a complication of COVID-19 vaccine, but implies its clinical manifestations may be varied and even may happen after the single dose of vaccination.


Subject(s)
COVID-19 Vaccines/adverse effects , Long QT Syndrome/etiology , Syncope/etiology , Aged , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/etiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Electrocardiography , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/drug therapy , Magnesium/administration & dosage , Male , Myocarditis/diagnosis , Myocarditis/etiology , Syncope/diagnosis , Vaccination/adverse effects , Vaccination/methods
3.
PLoS Med ; 18(9): e1003766, 2021 09.
Article in English | MEDLINE | ID: covidwho-1470656

ABSTRACT

BACKGROUND: Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial. METHODS AND FINDINGS: Studies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression. The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (-1.2 ms, -3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented. CONCLUSIONS: While caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate-reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.


Subject(s)
Amodiaquine/adverse effects , Antimalarials/adverse effects , Bradycardia/chemically induced , Heart Conduction System/drug effects , Heart Rate/drug effects , Long QT Syndrome/chemically induced , Adolescent , Adult , Bradycardia/diagnosis , Bradycardia/physiopathology , Cardiotoxicity , Child , Child, Preschool , Female , Heart Conduction System/physiopathology , Humans , Infant , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Male , Middle Aged , Randomized Controlled Trials as Topic , Risk Assessment , Risk Factors , Young Adult
4.
5.
Glob Heart ; 16(1): 42, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1285504

ABSTRACT

Background: QTc prolongation is an adverse effect of COVID-19 therapies. The use of a handheld device in this scenario has not been addressed. Objectives: To evaluate the feasibility of QTc monitoring with a smart device in COVID-19 patients receiving QTc-interfering therapies. Methods: Prospective study of consecutive COVID-19 patients treated with hydroxychloroquine ± azithromycin ± lopinavir-ritonavir. ECG monitoring was performed with 12-lead ECG or with KardiaMobile-6L. Both registries were also sequentially obtained in a cohort of healthy patients. We evaluated differences in QTc in COVID-19 patients between three different monitoring strategies: 12-lead ECG at baseline and follow-up (A), 12-lead ECG at baseline and follow-up with the smart device (B), and fully monitored with handheld 6-lead ECG (group C). Time needed to obtain an ECG registry was also documented. Results: One hundred and eighty-two COVID-19 patients were included (A: 119(65.4%); B: 50(27.5%); C: 13(7.1%). QTc peak during hospitalization did significantly increase in all groups. No differences were observed between the three monitoring strategies in QTc prolongation (p = 0.864). In the control group, all but one ECG registry with the smart device allowed QTc measurement and mean QTc did not differ between both techniques (p = 0.612), displaying a moderate reliability (ICC 0.56 [0.19-0.76]). Time of ECG registry was significantly longer for the 12-lead ECG than for handheld device in both cohorts (p < 0.001). Conclusion: QTc monitoring with KardiaMobile-6L in COVID-19 patients was feasible. Time of ECG registration was significantly lower with the smart device, which may offer an important advantage for prevention of virus dissemination among healthcare providers.


Subject(s)
COVID-19/drug therapy , Electrocardiography/methods , Long QT Syndrome/diagnosis , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Antiviral Agents/adverse effects , Azithromycin/adverse effects , Drug Combinations , Electrocardiography/instrumentation , Enzyme Inhibitors/adverse effects , Feasibility Studies , Female , Humans , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Lopinavir/adverse effects , Male , Middle Aged , Point-of-Care Systems , Prospective Studies , Reproducibility of Results , Ritonavir/adverse effects , SARS-CoV-2
6.
Cardiol J ; 28(3): 358-359, 2021.
Article in English | MEDLINE | ID: covidwho-1256940
8.
Europace ; 23(7): 1124-1133, 2021 07 18.
Article in English | MEDLINE | ID: covidwho-1233851

ABSTRACT

AIMS: Coronavirus disease of 2019 (COVID-19) has rapidly become a worldwide pandemic. Many clinical trials have been initiated to fight the disease. Among those, hydroxychloroquine and azithromycin had initially been suggested to improve clinical outcomes. Despite any demonstrated beneficial effects, they are still in use in some countries but have been reported to prolong the QT interval and induce life-threatening arrhythmia. Since a significant proportion of the world population may be treated with such COVID-19 therapies, evaluation of the arrhythmogenic risk of any candidate drug is needed. METHODS AND RESULTS: Using the O'Hara-Rudy computer model of human ventricular wedge, we evaluate the arrhythmogenic potential of clinical factors that can further alter repolarization in COVID-19 patients in addition to hydroxychloroquine (HCQ) and azithromycin (AZM) such as tachycardia, hypokalaemia, and subclinical to mild long QT syndrome. Hydroxychloroquine and AZM drugs have little impact on QT duration and do not induce any substrate prone to arrhythmia in COVID-19 patients with normal cardiac repolarization reserve. Nevertheless, in every tested condition in which this reserve is reduced, the model predicts larger electrocardiogram impairments, as with dofetilide. In subclinical conditions, the model suggests that mexiletine limits the deleterious effects of AZM and HCQ. CONCLUSION: By studying the HCQ and AZM co-administration case, we show that the easy-to-use O'Hara-Rudy model can be applied to assess the QT-prolongation potential of off-label drugs, beyond HCQ and AZM, in different conditions representative of COVID-19 patients and to evaluate the potential impact of additional drug used to limit the arrhythmogenic risk.


Subject(s)
COVID-19 , Long QT Syndrome , Azithromycin/adverse effects , COVID-19/drug therapy , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Humans , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , SARS-CoV-2
9.
J Electrocardiol ; 67: 1-6, 2021.
Article in English | MEDLINE | ID: covidwho-1222930

ABSTRACT

BACKGROUND: Minimizing direct patient contact among healthcare personnel is crucial for mitigating infectious risk during the coronavirus disease 2019 (COVID-19) pandemic. The use of remote cardiac telemetry as an alternative to 12­lead electrocardiography (ECG) for continuous QTc monitoring may facilitate this strategy, but its application has not yet been validated or implemented. METHODS: In the validation component of this two-part prospective cohort study, a total of 65 hospitalized patients with simultaneous ECG and telemetry were identified. QTc obtained via remote telemetry as measured by 3 independent, blinded operators were compared with ECG as assessed by 2 board-certified electrophysiologists as the gold-standard. Pearson correlation coefficients were calculated to measure the strength of linear correlation between the two methods. In a separate cohort comprised of 68 COVID-19 patients treated with combined hydroxychloroquine and azithromycin, telemetry-based QTc values were compared at serial time points after medication administration using Friedman rank-sum test of repeated measures. RESULTS: Telemetry-based QTc measurements highly correlated with QTc values derived from ECG, with correlation coefficients of 0.74, 0.79, 0.85 (individual operators), and 0.84 (mean of all operators). Among the COVID-19 cohort, treatment led to a median QTc increase of 15 milliseconds between baseline and following the 9th dose (p = 0.002), with 8 (12%) patients exhibiting an increase in QTc ≥ 60 milliseconds and 4 (6%) developing QTc ≥ 500 milliseconds. CONCLUSIONS: Cardiac telemetry is a validated clinical tool for QTc monitoring that may serve an expanding role during the COVID-19 pandemic strengthened by its remote and continuous monitoring capability and ubiquitous presence throughout hospitals.


Subject(s)
COVID-19 , Long QT Syndrome , Delivery of Health Care , Electrocardiography , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Pandemics , Prospective Studies , SARS-CoV-2 , Telemetry
10.
Ann Noninvasive Electrocardiol ; 26(5): e12853, 2021 09.
Article in English | MEDLINE | ID: covidwho-1220259

ABSTRACT

INTRODUCTION: 2019 novel coronavirus (COVID-19) patients frequently develop QT interval prolongation that predisposes them to Torsades de Pointes and sudden cardiac death. Continuous cardiac monitoring has been recommended for any COVID-19 patient with a Tisdale Score of seven or more. This recommendation, however, has not been validated. METHODS: We included 178 COVID-19 patients admitted to a non-intensive care unit setting of a tertiary academic medical center. A receiver operating characteristics curve was plotted to determine the accuracy of the Tisdale Score to predict QT interval prolongation. Multivariable analysis was performed to identify additional predictors. RESULTS: The area under the curve of the Tisdale Score was 0.60 (CI 95%, 0.46-0.75). Using the cutoff of seven to stratify COVID-19, patients had a sensitivity of 85.7% and a specificity of 7.6%. Risk factors independently associated with QT interval prolongation included a history of end-stage renal disease (ESRD) (OR, 6.42; CI 95%, 1.28-32.13), QTc ≥450 ms on admission (OR, 5.90; CI 95%, 1.62-21.50), and serum potassium ≤3.5 mmol/L during hospitalization (OR, 4.97; CI 95%, 1.51-16.36). CONCLUSION: The Tisdale Score is not a useful tool to stratify hospitalized non-critical COVID-19 patients based on their risks of developing QT interval prolongation. Clinicians should initiate continuous cardiac monitoring for patients who present with a history of ESRD, QTc ≥450 ms on admission or serum potassium ≤3.5 mmol/L.


Subject(s)
COVID-19/complications , Electrocardiography/methods , Long QT Syndrome/complications , Long QT Syndrome/diagnosis , Female , Humans , Length of Stay/statistics & numerical data , Long QT Syndrome/physiopathology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Sensitivity and Specificity
11.
JAMA Netw Open ; 4(4): e216842, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1198342

ABSTRACT

Importance: Critical illness, a marked inflammatory response, and viruses such as SARS-CoV-2 may prolong corrected QT interval (QTc). Objective: To evaluate baseline QTc interval on 12-lead electrocardiograms (ECGs) and ensuing changes among patients with and without COVID-19. Design, Setting, and Participants: This cohort study included 3050 patients aged 18 years and older who underwent SARS-CoV-2 testing and had ECGs at Columbia University Irving Medical Center from March 1 through May 1, 2020. Patients were analyzed by treatment group over 5 days, as follows: hydroxychloroquine with azithromycin, hydroxychloroquine alone, azithromycin alone, and neither hydroxychloroquine nor azithromycin. ECGs were manually analyzed by electrophysiologists masked to COVID-19 status. Multivariable modeling evaluated clinical associations with QTc prolongation from baseline. Exposures: COVID-19, hydroxychloroquine, azithromycin. Main Outcomes and Measures: Mean QTc prolongation, percentage of patients with QTc of 500 milliseconds or greater. Results: A total of 965 patients had more than 2 ECGs and were included in the study, with 561 (58.1%) men, 198 (26.2%) Black patients, and 191 (19.8%) aged 80 years and older. There were 733 patients (76.0%) with COVID-19 and 232 patients (24.0%) without COVID-19. COVID-19 infection was associated with significant mean QTc prolongation from baseline by both 5-day and 2-day multivariable models (5-day, patients with COVID-19: 20.81 [95% CI, 15.29 to 26.33] milliseconds; P < .001; patients without COVID-19: -2.01 [95% CI, -17.31 to 21.32] milliseconds; P = .93; 2-day, patients with COVID-19: 17.40 [95% CI, 12.65 to 22.16] milliseconds; P < .001; patients without COVID-19: 0.11 [95% CI, -12.60 to 12.81] milliseconds; P = .99). COVID-19 infection was independently associated with a modeled mean 27.32 (95% CI, 4.63-43.21) millisecond increase in QTc at 5 days compared with COVID-19-negative status (mean QTc, with COVID-19: 450.45 [95% CI, 441.6 to 459.3] milliseconds; without COVID-19: 423.13 [95% CI, 403.25 to 443.01] milliseconds; P = .01). More patients with COVID-19 not receiving hydroxychloroquine and azithromycin had QTc of 500 milliseconds or greater compared with patients without COVID-19 (34 of 136 [25.0%] vs 17 of 158 [10.8%], P = .002). Multivariable analysis revealed that age 80 years and older compared with those younger than 50 years (mean difference in QTc, 11.91 [SE, 4.69; 95% CI, 2.73 to 21.09]; P = .01), severe chronic kidney disease compared with no chronic kidney disease (mean difference in QTc, 12.20 [SE, 5.26; 95% CI, 1.89 to 22.51; P = .02]), elevated high-sensitivity troponin levels (mean difference in QTc, 5.05 [SE, 1.19; 95% CI, 2.72 to 7.38]; P < .001), and elevated lactate dehydrogenase levels (mean difference in QTc, 5.31 [SE, 2.68; 95% CI, 0.06 to 10.57]; P = .04) were associated with QTc prolongation. Torsades de pointes occurred in 1 patient (0.1%) with COVID-19. Conclusions and Relevance: In this cohort study, COVID-19 infection was independently associated with significant mean QTc prolongation at days 5 and 2 of hospitalization compared with day 0. More patients with COVID-19 had QTc of 500 milliseconds or greater compared with patients without COVID-19.


Subject(s)
Azithromycin , COVID-19 , Electrocardiography , Hydroxychloroquine , Long QT Syndrome , Aged, 80 and over , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19 Testing/methods , Drug Therapy, Combination/methods , Drug Therapy, Combination/statistics & numerical data , Electrocardiography/methods , Electrocardiography/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Long QT Syndrome/virology , Male , Middle Aged , New York/epidemiology , Outcome and Process Assessment, Health Care , Risk Factors , SARS-CoV-2 , Time Factors
12.
Circulation ; 143(13): 1274-1286, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1180993

ABSTRACT

BACKGROUND: Heart rate-corrected QT interval (QTc) prolongation, whether secondary to drugs, genetics including congenital long QT syndrome, and/or systemic diseases including SARS-CoV-2-mediated coronavirus disease 2019 (COVID-19), can predispose to ventricular arrhythmias and sudden cardiac death. Currently, QTc assessment and monitoring relies largely on 12-lead electrocardiography. As such, we sought to train and validate an artificial intelligence (AI)-enabled 12-lead ECG algorithm to determine the QTc, and then prospectively test this algorithm on tracings acquired from a mobile ECG (mECG) device in a population enriched for repolarization abnormalities. METHODS: Using >1.6 million 12-lead ECGs from 538 200 patients, a deep neural network (DNN) was derived (patients for training, n = 250 767; patients for testing, n = 107 920) and validated (n = 179 513 patients) to predict the QTc using cardiologist-overread QTc values as the "gold standard". The ability of this DNN to detect clinically-relevant QTc prolongation (eg, QTc ≥500 ms) was then tested prospectively on 686 patients with genetic heart disease (50% with long QT syndrome) with QTc values obtained from both a 12-lead ECG and a prototype mECG device equivalent to the commercially-available AliveCor KardiaMobile 6L. RESULTS: In the validation sample, strong agreement was observed between human over-read and DNN-predicted QTc values (-1.76±23.14 ms). Similarly, within the prospective, genetic heart disease-enriched dataset, the difference between DNN-predicted QTc values derived from mECG tracings and those annotated from 12-lead ECGs by a QT expert (-0.45±24.73 ms) and a commercial core ECG laboratory [10.52±25.64 ms] was nominal. When applied to mECG tracings, the DNN's ability to detect a QTc value ≥500 ms yielded an area under the curve, sensitivity, and specificity of 0.97, 80.0%, and 94.4%, respectively. CONCLUSIONS: Using smartphone-enabled electrodes, an AI DNN can predict accurately the QTc of a standard 12-lead ECG. QTc estimation from an AI-enabled mECG device may provide a cost-effective means of screening for both acquired and congenital long QT syndrome in a variety of clinical settings where standard 12-lead electrocardiography is not accessible or cost-effective.


Subject(s)
Artificial Intelligence , Electrocardiography/methods , Heart Diseases/diagnosis , Heart Rate/physiology , Adult , Aged , Area Under Curve , COVID-19/physiopathology , COVID-19/virology , Electrocardiography/instrumentation , Female , Heart Diseases/physiopathology , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Male , Middle Aged , Prospective Studies , ROC Curve , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Smartphone
13.
Pacing Clin Electrophysiol ; 44(5): 875-882, 2021 05.
Article in English | MEDLINE | ID: covidwho-1166232

ABSTRACT

BACKGROUND: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc). METHOD: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19. RESULTS: Patients who died were older than survivors (82 vs 69.8 years, p < 0.001), more likely to have cancer (22.3% vs 13.1%, p = 0.034), dementia (25.6% vs 10.7%, p = 0.034) and ischemic heart disease (27.8% vs 10.7%, p < 0.001). Deceased patients exhibited higher levels of C-reactive protein (244.6 mg/L vs 146.5 mg/L, p < 0.01), troponin (1982.4 ng/L vs 413.4 ng/L, p = 0.017), with a significantly longer QTc interval (461.1 ms vs 449.3 ms, p = 0.007). Pre-COVID electrocardiograms were located for 172 patients; the QTc recorded on presentation with COVID-19 was longer than the prior measurement in both groups, but was more prolonged in the deceased group (448.4 ms vs 472.9 ms, pre-COVID vs COVID, p < 0.01). Multivariate Cox-regression analysis revealed age, C-reactive protein and prolonged QTc of >455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]). CONCLUSION: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.


Subject(s)
COVID-19 , Long QT Syndrome , Azithromycin , Electrocardiography , Female , Humans , Hydroxychloroquine , Long QT Syndrome/diagnosis , Male , Prognosis , SARS-CoV-2
14.
BMC Cardiovasc Disord ; 21(1): 158, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1159221

ABSTRACT

INTRODUCTION: The cause-and-effect relationship of QTc prolongation in Coronavirus disease 2019 (COVID-19) patients has not been studied well. OBJECTIVE: We attempt to better understand the relationship of QTc prolongation in COVID-19 patients in this study. METHODS: This is a retrospective, hospital-based, observational study. All patients with normal baseline QTc interval who were hospitalized with the diagnosis of COVID-19 infection at two hospitals in Ohio, USA were included in this study. RESULTS: Sixty-nine patients had QTc prolongation, and 210 patients continued to have normal QTc during hospitalization. The baseline QTc intervals were comparable in the two groups. Patients with QTc prolongation were older (mean age 67 vs. 60, P 0.003), more likely to have underlying cardiovascular disease (48% versus 26%, P 0.001), ischemic heart disease (29% versus 17%, P 0.026), congestive heart failure with preserved ejection fraction (16% versus 8%, P 0.042), chronic kidney disease (23% versus 10%, P 0.005), and end-stage renal disease (12% versus 1%, P < 0.001). Patients with QTc prolongation were more likely to have received hydroxychloroquine (75% versus 59%, P 0.018), azithromycin (18% vs. 14%, P 0.034), a combination of hydroxychloroquine and azithromycin (29% vs 7%, P < 0.001), more than 1 QT prolonging agents (59% vs. 32%, P < 0.001). Patients who were on angiotensin-converting enzyme inhibitors (ACEi) were less likely to develop QTc prolongation (11% versus 26%, P 0.014). QTc prolongation was not associated with increased ventricular arrhythmias or mortality. CONCLUSION: Older age, ESRD, underlying cardiovascular disease, potential virus mediated cardiac injury, and drugs like hydroxychloroquine/azithromycin, contribute to QTc prolongation in COVID-19 patients. The role of ACEi in preventing QTc prolongation in COVID-19 patients needs to be studied further.


Subject(s)
COVID-19/drug therapy , Cardiovascular Diseases/epidemiology , Electrocardiography , Long QT Syndrome , Renal Insufficiency, Chronic/epidemiology , Age Factors , Aged , COVID-19/classification , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , Comorbidity , Correlation of Data , Electrocardiography/methods , Electrocardiography/statistics & numerical data , Female , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Long QT Syndrome/etiology , Male , Middle Aged , Outcome and Process Assessment, Health Care , Risk Assessment/methods , SARS-CoV-2/isolation & purification , Survival Analysis , United States/epidemiology
16.
Anticancer Drugs ; 32(5): 589-591, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1082921

ABSTRACT

Encorafenib (Braftovi) is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation, in combination with binimetinib (Mektovi). According to the product label of encorafenib, there are no specific treatment recommendations in case of an overdose. We report on a 63-year-old man who ingested a double dose (900 mg) of encorafenib for 16 days. He developed overall minor chronic overdose symptoms such as nausea and vomiting grade 1 and muscle pain. Based on the most occurring adverse events of encorafenib, liver values, kidney function parameters and QTc interval were measured. Kidney function parameters were normal, whereas liver values were slightly increased (grade 1) and QTc slightly prolonged. The plasma concentration 3 h after the last dose was 2110 ng/mL. We describe the course of a case with a chronic overdose during 16 days of the double dose of encorafenib as well as the followed approach, which could be taken into account when observing an encorafenib overdose. Providing information in times of Covid-19 is challenging, but remains necessary for good clinical care.


Subject(s)
Carbamates , Drug Overdose , Liver Function Tests/methods , Long QT Syndrome , Medication Therapy Management/standards , Melanoma , Skin Neoplasms , Sulfonamides , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , COVID-19/epidemiology , Carbamates/administration & dosage , Carbamates/adverse effects , Carbamates/blood , Communicable Disease Control , Dose-Response Relationship, Drug , Drug Monitoring/methods , Drug Overdose/blood , Drug Overdose/diagnosis , Drug Overdose/etiology , Drug Overdose/physiopathology , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Male , Melanoma/drug therapy , Melanoma/genetics , Melanoma/pathology , Middle Aged , Mutation , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/drug therapy , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Sulfonamides/blood , Vomiting/chemically induced , Vomiting/diagnosis
18.
Int J Cardiol ; 324: 255-260, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1065148

ABSTRACT

The antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19. Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious. Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%. These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly.


Subject(s)
COVID-19/drug therapy , COVID-19/epidemiology , Cardiotoxicity/epidemiology , Lopinavir/administration & dosage , Lopinavir/adverse effects , Pharmacovigilance , Ritonavir/administration & dosage , Ritonavir/adverse effects , Aged , Aged, 80 and over , COVID-19/diagnosis , Cardiotoxicity/diagnosis , Drug Combinations , Electrocardiography/drug effects , Electrocardiography/trends , Female , France/epidemiology , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/adverse effects , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Male , Middle Aged , Potassium Channel Blockers/administration & dosage , Potassium Channel Blockers/adverse effects
19.
Int J Cardiol ; 324: 242-248, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1065146

ABSTRACT

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. METHOD: A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). RESULTS: A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented. CONCLUSIONS: The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.


Subject(s)
Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19/chemically induced , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Long QT Syndrome/drug therapy , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Antimalarials/administration & dosage , Antimalarials/adverse effects , COVID-19/diagnosis , COVID-19/physiopathology , Drug Therapy, Combination , Electrocardiography/drug effects , Electrocardiography/trends , Female , Follow-Up Studies , Humans , Long QT Syndrome/diagnosis , Male , Middle Aged , Patient Safety , Retrospective Studies
20.
Circulation ; 143(13): 1274-1286, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1058120

ABSTRACT

BACKGROUND: Heart rate-corrected QT interval (QTc) prolongation, whether secondary to drugs, genetics including congenital long QT syndrome, and/or systemic diseases including SARS-CoV-2-mediated coronavirus disease 2019 (COVID-19), can predispose to ventricular arrhythmias and sudden cardiac death. Currently, QTc assessment and monitoring relies largely on 12-lead electrocardiography. As such, we sought to train and validate an artificial intelligence (AI)-enabled 12-lead ECG algorithm to determine the QTc, and then prospectively test this algorithm on tracings acquired from a mobile ECG (mECG) device in a population enriched for repolarization abnormalities. METHODS: Using >1.6 million 12-lead ECGs from 538 200 patients, a deep neural network (DNN) was derived (patients for training, n = 250 767; patients for testing, n = 107 920) and validated (n = 179 513 patients) to predict the QTc using cardiologist-overread QTc values as the "gold standard". The ability of this DNN to detect clinically-relevant QTc prolongation (eg, QTc ≥500 ms) was then tested prospectively on 686 patients with genetic heart disease (50% with long QT syndrome) with QTc values obtained from both a 12-lead ECG and a prototype mECG device equivalent to the commercially-available AliveCor KardiaMobile 6L. RESULTS: In the validation sample, strong agreement was observed between human over-read and DNN-predicted QTc values (-1.76±23.14 ms). Similarly, within the prospective, genetic heart disease-enriched dataset, the difference between DNN-predicted QTc values derived from mECG tracings and those annotated from 12-lead ECGs by a QT expert (-0.45±24.73 ms) and a commercial core ECG laboratory [10.52±25.64 ms] was nominal. When applied to mECG tracings, the DNN's ability to detect a QTc value ≥500 ms yielded an area under the curve, sensitivity, and specificity of 0.97, 80.0%, and 94.4%, respectively. CONCLUSIONS: Using smartphone-enabled electrodes, an AI DNN can predict accurately the QTc of a standard 12-lead ECG. QTc estimation from an AI-enabled mECG device may provide a cost-effective means of screening for both acquired and congenital long QT syndrome in a variety of clinical settings where standard 12-lead electrocardiography is not accessible or cost-effective.


Subject(s)
Artificial Intelligence , Electrocardiography/methods , Heart Diseases/diagnosis , Heart Rate/physiology , Adult , Aged , Area Under Curve , COVID-19/physiopathology , COVID-19/virology , Electrocardiography/instrumentation , Female , Heart Diseases/physiopathology , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Male , Middle Aged , Prospective Studies , ROC Curve , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Smartphone
SELECTION OF CITATIONS
SEARCH DETAIL
...