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Objective: To analyze the clinical characteristics of fatal cardiac adverse events associated with chloroquine, which was recommended for the antiviral treatment of novel coronavirus pneumonia, and provide reference for clinical safe drug use. Method(s): The fatal cardiac adverse events associated with chloroquine were searched from the World Health Organization global database of individual case safety reports (VigiBase). The clinical characteristics of the individual cases with well-documented reports (VigiGrade completeness score >=0.80 or with detailed original reports) were analyzed. The adverse events were coded using the systematic organ classification (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) version 22.1 of International Conference on Harmonization (ICH). Result(s): Up to 23 February 2020, a total of 45 reports of fatal heart injuries related to chloroquine were reported in VigiBase, which were from 16 countries. Of them, 30 reports were fully informative. Among the 30 reports,20 cases developed fatal cardiac adverse events after a single large dose of chloroquine. Of them, 17 cases' fatal cardiac adverse events were caused by overdose of chloroquine (15 cases were suicide or suspected suicide, and 2 children took chloroquine by mistake);3 cases' fatal cardiac adverse events were caused in clinical treatment;18 cases showed arrhythmia and cardiac arrest;6 cases showed prolonged QRS wave or QT interval;6 cases were with hypokalemia, including 4 severe ones. Among the 30 reports, 10 cases developed fatal cardiac adverse events after multiple administration of chloroquine, of which 4 cases were treated with chloroquine for 23 days to 2 months and died of heart failure, cardiac arrest or myocardial infarction;6 cases were treated with chloroquine for 20 months to 29 years and all of them had cardiomyopathy, which were confirmed by endomyocardial biopsy to be caused by chloroquine in 3 cases. Conclusion(s): Cardiac toxicity was the primary cause of fatal adverse events caused by chloroquine;the main manifestation of single large dose of chloroquine was arrhythmia and the manifestation of multiple administration was cardiomyopathy.Copyright © 2020 by the Chinese Medical Association.
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Background: The impact of SARS-CoV-2 infection on intrinsic myocardial conduction continues to be an area of focus amongst the medical community. Our objective was to investigate if specific myocardial conduction abnormalities were independently associated with mortality in patients hospitalized with COVID 19. Method(s): Under IRB exemption, the electronic medical records of COVID-19 patients (N=3840) undergoing index hospitalization were reviewed to extract presentation ECG conduction data, demographics, and laboratory results (within 8h). This patient cohort was then separated into two groups based on mortality vs. no mortality (N=520). Logistical regression was used to test association of ECG conduction intervals with mortality. A subgroup analysis of 651 patients who underwent at least 1 ECG in the 12 months prior to their COVID hospitalization were analyzed to detect statistically significant differences in conduction intervals pre and post SARS-CoV-2 infection. Result(s): According to our nominal logistic fit for hospital mortality, Heart Rate (HR) >100 (p=0.0007;LW 4.14), QRS duration > 120 ms (p=0.0053;LW 2.27), and QTc prolongation (defined as QTc > 450ms in males;QTc > 460ms in females) (p=0.0089;LW 2.04) were independently associated with higher risk of mortality. LogWorth (LW) calculations were included in an effort to estimate the proportional effect each variable has on overall mortality. LW > 2 were shown to be statistically significant with p< 0.05 with HR > 100 (LW 4.14) having the highest proportional effect on mortality followed by QRSd (LW 2.27) then QTc prolongation (LW 2.04). PR interval> 200ms (p=0.30) and QRS axis (p=0.15) were not associated with higher risk of mortality. Our subgroup analysis of the 651 patients mentioned above yielded no statistically significant differences in conduction intervals pre & post SARS-CoV-2 infection. Conclusion(s): : Amongst our patient cohort, HR > 100, QRSd > 120ms, and QTc prolongation (QTc > 450 in males;QTc > 460 in females) were each independently associated with higher risk of mortality in patients hospitalized with COVID 19. Subgroup analysis of 651 patients showed no statistically significant differences in conduction intervals pre and post SARS-CoV-2 infection. These findings support the use of objective ECG data in risk stratifying patients hospitalized with COVID 19.Copyright © 2022
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Objective: Covid-19 infection has been declared as a pandemic disease by the World Health Organization (WHO) and has been associated with increased morbidity and mortality. More than 400 million people diagnosed with the disease has been reported until February 2022 [1]. Covid-19 infection mostly progresses with lung involvement and pneumonia, however, its effects on the cardiovascular system are also well-known. Studies have reported that Covid 19 infection can trigger cardiac events such as acute myocardial damage, acute myocarditis, acute coronary syndrome (ACS), ventricular arrhythmias, cardiogenic shock, and cardiac arrest [2]. Electrocardiogram (ECG) is an important tool to diagnose cardiac involvement. QTc interval, QT dispersion, Tp-e interval, Tp-e/QTc ratio are defined as ventricular repolarization parameters and these parameters are associated with increased risk of ventricular arrhythmia [3,4]. In our study, we aimed to evaluate to predict ventricular arrhythmia by ECG in Covid-19 patients. Method(s): Our study is a single-center, cross-sectional study. Patients diagnosed with Covid-19 in our center between July and October 2020 were included. 408 patients with positive SARS-CoV2 PCR test were detected and the ECGs of the patients were recorded at admission and 15 days after symptomatic recovery. After the exclusion criteria, remained 91 patients were analyzed. Conduction parameters (PR and QRS durations) and repolarization parameters (QTc interval, QT dispersion, Tp-e interval and Tp-e/QTc ratio) were evaluated in 12-lead ECG recordings. Result(s): Ninety-one patients with Covid-19 infection were included. The group were consisted of 47 male (52%) and 44 female (48%). The mean age was 50.4 years. As a result of the statistical analysis, no significant difference was observed between the groups in terms of PR interval (142.2+/-21.4 ms vs. 140.1+/-19.0 ms;p=0.312). QRS duration was found significantly higher during active infection (91.4+/-12.2 ms vs. 88.8+/-10.9 ms;p=0.022). The mean QTc duration was detected longer in the first ECG, but no statistically significant difference was observed between the two groups (426.1+/-23.6 ms vs. 422.5+/-26.2 ms;p=0.237). QT dispersion (35.2+/-7.3 ms vs. 27.7+/-7.8 ms;p<0.001), Tp-e interval (86.7+/-10.1 ms vs. 76.1+/-9.9 ms;p<0.001) and Tp-e/QTc ratio (0.204+/-0.026 vs 0.180+/-0.025;p<0.001) were found significantly higher during active infection Conclusion(s): In our study, QRS complex, QT dispersion, Tp-e interval, Tpe/ QTc ratio were significantly higher during active infection. We considered these parameters as a contributor of the increased mortality by inducing ventricular arrhythmia and sudden death in Covid-19 patients during active infection.
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Objectives: To study the clinico-electrophysiological profile of patients with Infrahisian Wenckebach (IHW) conduction. Material(s) and Method(s): Patients with a clinical diagnosis of atrioventricular (AV) block who underwent permanent pacemaker implantation (PPI) based on standard indications from July 2021-June 2022 at The Madras Medical Mission were subjected to pre-implant Electrophysiology study to document conduction pathology. Result(s): A total of 94 patients underwent PPI for AV block during the study period. EPS was performed in all but one patient (COVID pneumonia). The incidence of IHW was 9/93 (9.6%) of patients with AV block. There is no gender predisposition (M-4, F-5) and their mean age was 71.4 +/- 11.7 years. As many as half of the patients (5/9) had an underlying narrow QRS. The mean QRS duration was 130 +/- 19.3. Ischemic heart disease affected half of the patients and cardiomyopathy in 4/9 patients (mean EF 45.1 +/- 13.7%). Presentation was syncope in all, mean NYHA class was 2.1. Presentation ranged from isolated 1st-degree AV block (1/9) to tri-fascicular block (3/9). In EP study, the mean basal HV interval was 94.7 +/- 27.1 ms. IHW was noted spontaneously in 4 patients and on atrial pacing in the remaining. In the literature, a total of 11 documented cases have been reported (8 case reports). Unlike typical Wenckebach, the increment in PRI is minimal in the 2nd beat of the train. Conclusion(s): Wenckebach periodicity is classically considered an AV nodal phenomenon. IHW is scarcely reported in the literature. Distinction becomes critical as IHW is harbinger of a complete AV block. This is the largest series and the first clinic-etiological profile of IHW patients published to date.
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BACKGROUND: The impact of SARS-CoV-2 infection on intrinsic myocardial conduction continues to be an area of focus amongst the medical community. Our objective was to investigate if specific myocardial conduction abnormalities were independently associated with mortality in patients hospitalized with COVID 19. METHODS: Under IRB exemption, the electronic medical records of COVID-19 patients (N=3840) undergoing index hospitalization were reviewed to extract presentation ECG conduction data, demographics, and laboratory results (within 8h). This patient cohort was then separated into two groups based on mortality vs. not (N=520). Logistical regression was used to test association of ECG conduction intervals with mortality. RESULTS: According to our nominal logistic fit for hospital mortality, Heart Rate (HR) >100 (p=0.0007;LW 4.14), QRS duration > 120 ms (p=0.0053;LW 2.27), and QTc prolongation (defined as QTc > 450ms in males;QTc > 460ms in females) (p=0.0089;LW 2.04) were independently associated with higher risk of mortality. LogWorth (LW) calculations were included in an effort to estimate the proportional effect each variable has on overall mortality. LW > 2 were shown to be statistically significant with p< 0.05 with HR > 100 (LW 4.14) having the highest proportional effect on mortality followed by QRSd (LW 2.27) then QTc prolongation (LW 2.04). PR interval> 200ms (p=0.30) and QRS axis (p=0.15) were not associated with higher risk of mortality. CONCLUSIONS: Amongst our patient cohort, HR > 100, QRSd > 120ms, and QTc prolongation (QTc > 450 in males;QTc > 460 in females) were each independently associated with higher risk of mortality in patients hospitalized with COVID 19. These findings support the use of objective ECG data in risk stratifying patients hospitalized with COVID 19.
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Background: With increasing utilisation of transcatheter aortic valve implantation (TAVI) for aortic stenosis, there is a need to explore the safety of next-day discharge. We aimed to evaluate the safety and outcomes of next-day discharge following TAVI. Methods: We performed a retrospective analysis of patients who underwent TAVI at a tertiary centre between 2020 and 2021. Included patients were those discharged the next day after TAVI as routine care. Data collected included baseline demographics, Society of Thoracic Surgeons (STS) score, perioperative complications and 30-day mortality rates. Results: Thirty-three patients (33% female, median age 82 years;interquartile range [IQR], 77–84) were discharged the next day post-TAVI. Median STS score was 2.3% (IQR, 1.7–3.6). On pre-TAVI ECG, two patients (6%) had right bundle branch block (QRS duration 147–154 ms). All patients demonstrated well-seated aortic valve prosthesis with no aortic regurgitation on same-day transthoracic echocardiogram. Six patients (18%) had new conduction abnormalities post-TAVI (five transient left bundle branch block, one atrial fibrillation which self-resolved). There were no significant procedural complications including no pericardial effusion or vascular injury. All patients were discharged directly home without the need for subacute care. Two patients (6%) were re-hospitalised within 30 days of discharge: one admitted with presyncope of unclear cause and one required a pacemaker for tachy-brady syndrome. All patients were alive and well at 30 days. Conclusion: We have demonstrated that next-day discharge TAVI is safe in selected patients with an uncomplicated procedure. In the era of COVID, implementation of next-day discharge can reduce unnecessary length of stay and may improve hospital resource allocation.
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Ensifentrine (RPL554) is an investigational, first-in-class, inhaled dual inhibitor of PDE 3 and 4 with bronchodilator and anti-inflammatory actions in a single compound administered via nebulizer. This reports on the results from a phase 1, randomized, double-blind, placebo- and positivecontrolled, 4-way crossover thorough QT (TQT) study in healthy individuals. Thirty-two male and female subjects were randomized to receive a single dose of blinded ensifentrine 3mg (therapeutic dose), 9 mg (supra-therapeutic dose), and placebo via standard jet nebulizer and a single dose of oral moxifloxacin (400 mcg, open-label) in 4 separate treatment periods. 12-lead electrocardiograms (ECGs) were extracted from continuous Holter recordings pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours post-dose. ECG parameters were measured by a blinded central ECG laboratory. The primary statistical method was concentration-QTc analysis with the placebo-corrected change-from-baseline QTcF (ΔΔQTcF) as the primary endpoint. No clinically relevant effect on ΔΔQTcF was observed with either the 3mg or 9mg dose of ensifentrine. Using concentration-QTc analysis, the effect on ΔΔQTcF at the geometric mean estimated Cmax of 3 mg (546 pg/mL) and 9 mg (2342 pg/mL) ensifentrine indicated 1.4 ms (90% CI: 0.4 to 2.4) and 3.7 ms (90% CI: 0.7 to 6.7) increases vs placebo, respectively. The by-timepoint analysis showed that all upper bounds of the 90% CIs of ΔΔQTcF were below 10 ms with both doses across all timepoints. The lower bound of the 90% CI of the predicted QTc effect at the moxifloxacin mean Cmax was above 5 ms, thereby demonstrating assay sensitivity. Ensifentrine did not have a clinically meaningful effect on heart rate, PR or QRS intervals with either dose. In healthy individuals, both doses of ensifentrine were well tolerated. There were 14 (14.3%) reported AEs, including 13 treatment-emergent AEs (TEAE) of which 1 TEAE was serious (syncope) approximately 2 days post-dose in a subject who was hospitalized following the syncope event and physical injuries from a subsequent fall. The subject was positive for COVID-19 (moderate AE) at the time of hospitalization for the SAE event, and this was the only TEAE that led to study discontinuation. All AEs were mild except for syncope (severe) and COVID-19 (moderate). There were no deaths. AEs (23.3%) were more frequently reported in the ensifentrine-9mg arm. In summary, ensifentrine at the studied doses had no clinically relevant effects on studied ECG parameters.
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Background: COVID-19 infection is known to damage myocardial tissue and increase arrhythmic events. However, the data in the literature on permanent attachments are limited. In our study, we planned to investigate possible arrhythmic damages in COVID-19 survivors using the frontal plane QRS-T [f(QRS)-T] angle and some other ECG parameters. Patients & Methods: 269 patients who recovered from COVID-19 between April 2020 and January 2021 were included into the study. Pre-admission electrocardiograms and first-month outpatient clinic control ECGs of the patients were compared. Results: After COVID-19, left bundle branch block (p<0.001), right bundle branch block (p<0.001), right bundle branch block (p<0.001), atrial fibrillation (p<0.001) rates had increased. Prolongation was detected in QRS duration (p<0.001), QT interval (p=0.014), adjusted QT interval (p =0.007) and Tpe interval (p=0.012). F(QRS)-T angle (p<0.001) and fragmented QRS rate (p<0.001) were increased. Conclusions: It was observed in our study that;even if patients survive after COVID-19, permanent deterioration in ECG parameters may occur.
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Introduction: Atrial fibrillation (Afib) is a common arrhythmia with significant morbidity and mortality. The cardiovascular effect of COVID-19 infection in patients with known Afib is poorly understood. The aim of this study was to analyze the cardiovascular outcomes of patients with a history of Afib who were admitted with COVID-19 infection. Methods: A retrospective cohort study of patients hospitalized between January 1 and July 31, 2020 with COVID-19 infection confirmed by polymerase chain reaction (PCR) testing of nasopharynx sample was stratified by history of Afib, and analyzed for patient characteristics and cardiovascular outcomes using Mann-Whitney & χ tests. A p value of <0.05 was used for statistical significance. Results: Among the 321 patients admitted with a positive COVID-19 test, 12% (38) had a history of Afib. This subgroup was significantly older, median age 84.5 vs. 61 and were predominantly male, 66 vs. 34%. They showed a higher prevalence of heart failure with reduced ejection fraction (HFrEF) (26 vs. 6%) and with preserved ejection fraction (HFpEF) (34 vs. 13%), CAD (34 vs. 17%), chronic kidney disease (45 vs. 20%), and dyslipidemia (66 vs. 35%) compared to those admitted without a history of Afib. These patients had a wider QRS interval 101 (88-134) vs. 94 (86-104) and more elevated BNP levels 278 (109-696.5) vs. 234 (35-158). They were also more likely to experience Afib (53 vs. 7%) and ventricular arrhythmias (18 vs. 6%) during hospitalization, but they did not show any statistical difference in terms of mortality rate, ICU admission, use of mechanical ventilation, or 30-day hospital readmission. Conclusion: Patients admitted with COVID-19 with a history of Afib were older and had comorbid cardiovascular disease. Heart failure risk markers such as wider QRS interval and higher BNP levels were more common in the history of Afib subgroup of patients. These patients had a higher incidence of heart failure and arrhythmias but not mortality.