Automatic detection of cardiac conditions from photos of electrocardiogram captured by smartphones.

BACKGROUND: Researchers have developed machine learning-based ECG diagnostic algorithms that match or even surpass cardiologist level of performance. However, most of them cannot be used in real-world, as older generation ECG machines do not permit installation of new algorithms. OBJECTIVE: To develop a smartphone application that automatically extract ECG waveforms from photos and to convert them to voltage-time series for downstream analysis by a variety of diagnostic algorithms built by researchers. METHODS: A novel approach of using objective detection and image segmentation models to automatically extract ECG waveforms from photos taken by clinicians was devised. Modular machine learning models were developed to sequentially perform waveform identification, gridline removal, and scale calibration. The extracted data were then analysed using a machine learning-based cardiac rhythm classifier. RESULTS: Waveforms from 40 516 scanned and 444 photographed ECGs were automatically extracted. 12 828 of 13 258 (96.8%) scanned and 5399 of 5743 (94.0%) photographed waveforms were correctly cropped and labelled. 11 604 of 12 735 (91.1%) scanned and 5062 of 5752 (88.0%) photographed waveforms achieved successful voltage-time signal extraction after automatic gridline and background noise removal. In a proof-of-concept demonstration, an atrial fibrillation diagnostic algorithm achieved 91.3% sensitivity, 94.2% specificity, 95.6% positive predictive value, 88.6% negative predictive value and 93.4% F1 score, using photos of ECGs as input. CONCLUSION: Object detection and image segmentation models allow automatic extraction of ECG signals from photos for downstream diagnostics. This novel pipeline circumvents the need for costly ECG hardware upgrades, thereby paving the way for large-scale implementation of machine learning-based diagnostic algorithms.

Post-COVID-19 vaccination myocarditis: a prospective cohort study pre and post vaccination using cardiovascular magnetic resonance.

BACKGROUND: Concerns about COVID-19 vaccination induced myocarditis or subclinical myocarditis persists in some populations. Cardiac magnetic resonance imaging (CMR) has been used to detect signs of COVID-19 vaccination induced myocarditis. This study aims to: (i) characterise myocardial tissue, function, size before and after COVID-19 vaccination, (ii) determine if there is imaging evidence of subclinical myocardial inflammation or injury after vaccination using CMR. METHODS: Subjects aged ≥ 12yrs old without prior COVID-19 or COVID-19 vaccination underwent two CMR examinations: first, ≤ 14 days before the first COVID-19 vaccination and a second time ≤ 14 days after the second COVID-19 vaccination. Biventricular indices, ejection fraction (EF), global longitudinal strain (GLS), late gadolinium enhancement (LGE), left ventricular (LV) myocardial native T1, T2, extracellular volume (ECV) quantification, lactate dehydrogenase (LDH), white cell count (WCC), C-reactive protein (CRP), NT-proBNP, troponin-T, electrocardiogram (ECG), and 6-min walk test were assessed in a blinded fashion. RESULTS: 67 subjects were included. First and second CMR examinations were performed a median of 4 days before the first vaccination (interquartile range 1-8 days) and 5 days (interquartile range 3-6 days) after the second vaccination respectively. No significant change in global native T1, T2, ECV, LV EF, right ventricular EF, LV GLS, LGE, ECG, LDH, troponin-T and 6-min walk test was demonstrated after COVID-19 vaccination. There was a significant WCC decrease (6.51 ± 1.49 vs 5.98 ± 1.65, p = 0.003) and CRP increase (0.40 ± 0.22 vs 0.50 ± 0.29, p = 0.004). CONCLUSION: This study found no imaging, biochemical or ECG evidence of myocardial injury or inflammation post COVID-19 vaccination, thus providing some reassurance that COVID-19 vaccinations do not typically cause subclinical myocarditis.

Volume markers in left ventricular diastolic dysfunction and adverse outcomes in peritoneal dialysis patients: a prospective cohort study.

Left ventricular diastolic dysfunction (LVDD) is an early event associated with cardiovascular complications and poor prognosis in chronic kidney disease patients undergoing dialysis. In this study, we investigated whether diastolic dysfunction, measured by the E/E' ratio, affects adverse outcomes in peritoneal dialysis (PD) patients (n = 148). Our results showed that patients with an E/E' ratio ≥ 15 were more likely to be female, have a longer dialysis vintage, have significantly higher left atrial volume index and left atrial kinetic energy levels, have lower E' levels and LV hypertrophy (LVH) degree, and have higher volume markers. Kaplan-Meier curves revealed that patients with a higher E/E' ratio had worse survival and a higher risk of heart failure than those with a lower E/E' ratio. Subgroup analysis demonstrated that non-diabetic patients with a higher E/E' ratio had a higher risk of heart failure than those with a lower E/E' ratio. Cox proportional hazard regression analysis indicated that the ECW/ICW ratio was strongly associated with LVDD and confirmed that the E/E' ratio was an independent risk factor for overall death. Our study suggests that monitoring the E/E' ratio in PD patients is important for improving their prognosis.

Clinical Outcomes of Left Atrial Appendage Occlusion Versus Switch of Direct Oral Antcoagulant in Atrial Fibrillation: A Territory-Wide Retrospective Analysis.

Background Left atrial appendage occlusion (LAAO) has emerged as an alternative to oral anticoagulation therapy for stroke prevention in atrial fibrillation, but data comparing LAAO with direct oral anticoagulant (DOAC) are sparse. Methods and Results This cohort study compared LAAO (with or without prior anticoagulation) with a switch of one DOAC to another DOAC by 1:2 propensity score matching. The primary outcome was a composite of all-cause mortality, ischemic stroke, and major bleeding. A total of 2350 patients (874 in the LAAO group and 1476 in the DOAC switch group) were included. After a mean follow-up of 1052±694 days, the primary outcome developed in 215 (24.6%) patients in the LAAO group and in 335 (22.7%) patients in the DOAC switch group (hazard ratio [HR], 0.94 [95% CI, 0.80-1.12]; P=0.516). The LAAO group had a lower all-cause mortality (HR, 0.49 [95% CI, 0.39-0.60]; P<0.001) and cardiovascular mortality (HR, 0.49 [95% CI, 0.32-0.73]; P<0.001) but similar risk of ischemic stroke (HR, 0.83 [95% CI, 0.63-1.10]; P=0.194). The major bleeding risk was similar overall (HR, 1.18 [95% CI, 0.94-1.48], P=0.150) but was lower in the LAAO group after 6 months (HR, 0.71 [95% CI, 0.51-0.97]; P=0.032). Conclusions LAAO conferred a similar risk of composite outcome of all-cause mortality, ischemic stroke, and major bleeding, as compared with DOAC switch. The risks of all-cause mortality and cardiovascular mortality were lower with LAAO.

Impact of Hemodialysis on Left Ventricular-Arterial Coupling in End-Stage Renal Disease Patients.

INTRODUCTION: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. METHODS: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. RESULTS: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. CONCLUSIONS: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.

Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Intraventricular 4D flow cardiovascular magnetic resonance for assessing patients with heart failure with preserved ejection fraction: a pilot study.

Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging. Intraventricular four-dimensional flow (4D flow) phase-contrast cardiovascular magnetic resonance (CMR) can assess different components of left ventricular (LV) flow including direct flow, delayed ejection, retained inflow and residual volume. This could be utilised to identify HFpEF. This study investigated if intraventricular 4D flow CMR could differentiate HFpEF patients from non-HFpEF and asymptomatic controls. Suspected HFpEF patients and asymptomatic controls were recruited prospectively. HFpEF patients were confirmed using European Society of Cardiology (ESC) 2021 expert recommendations. Non-HFpEF patients were diagnosed if suspected HFpEF patients did not fulfil ESC 2021 criteria. LV direct flow, delayed ejection, retained inflow and residual volume were obtained from 4D flow CMR images. Receiver operating characteristic (ROC) curves were plotted. 63 subjects (25 HFpEF patients, 22 non-HFpEF patients and 16 asymptomatic controls) were included in this study. 46% were male, mean age 69.8 ± 9.1 years. CMR 4D flow derived LV direct flow and residual volume could differentiate HFpEF vs combined group of non-HFpEF and asymptomatic controls (p < 0.001 for both) as well as HFpEF vs non-HFpEF patients (p = 0.021 and p = 0.005, respectively). Among the 4 parameters, direct flow had the largest area under curve (AUC) of 0.781 when comparing HFpEF vs combined group of non-HFpEF and asymptomatic controls, while residual volume had the largest AUC of 0.740 when comparing HFpEF and non-HFpEF patients. CMR 4D flow derived LV direct flow and residual volume show promise in differentiating HFpEF patients from non-HFpEF patients.

Case report: Coronavirus Disease 2019 (COVID-19) modified RNA vaccination-induced Adult-Onset Still's Disease with fulminant myocarditis as initial presentation.

Myocarditis is a rare complication of Coronavirus Disease 2019 (COVID-19) vaccination. We report a case of an elderly female who presented initially with acute myocarditis, fulminant heart failure, and atrial fibrillation after receiving a modified ribonucleic acid (mRNA) vaccine (BNT162b2). Unlike other patients with vaccine-induced myocarditis, she developed persistent fever, sore throat, polyarthralgia, diffuse macular rash, and lymphadenopathy. After extensive investigation, she was diagnosed with post-vaccination Adult-Onset Still's Disease. The systemic inflammation gradually subsided after the use of non-steroidal anti-inflammatory drugs and systemic steroids. She was discharged from hospital with stable hemodynamics. Methotrexate was subsequently given to maintain long-term remission.

Diagnostic accuracy of cardiovascular magnetic resonance strain analysis and atrial size to identify heart failure with preserved ejection fraction.

Aims: Heart failure with preserved ejection fraction (HFpEF) continues to be a diagnostic challenge. Cardiac magnetic resonance atrial measurement, feature tracking (CMR-FT), tagging has long been suggested to diagnose HFpEF and potentially complement echocardiography especially when echocardiography is indeterminate. Data supporting the use of CMR atrial measurements, CMR-FT or tagging, are absent. Our aim is to conduct a prospective case-control study assessing the diagnostic accuracy of CMR atrial volume/area, CMR-FT, and tagging to diagnose HFpEF amongst patients suspected of having HFpEF. Methods and results: One hundred and twenty-one suspected HFpEF patients were prospectively recruited from four centres. Patients underwent echocardiography, CMR, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements within 24 h to diagnose HFpEF. Patients without HFpEF diagnosis underwent catheter pressure measurements or stress echocardiography to confirm HFpEF or non-HFpEF. Area under the curve (AUC) was determined by comparing HFpEF with non-HFpEF patients. Fifty-three HFpEF (median age 78 years, interquartile range 74-82 years) and thirty-eight non-HFpEF (median age 70 years, interquartile range 64-76 years) were recruited. Cardiac magnetic resonance left atrial (LA) reservoir strain (ResS), LA area index (LAAi), and LA volume index (LAVi) had the highest diagnostic accuracy (AUCs 0.803, 0.815, and 0.776, respectively). Left atrial ResS, LAAi, and LAVi had significantly better diagnostic accuracy than CMR-FT left ventricle (LV)/right ventricle (RV) parameters and tagging (P < 0.01). Tagging circumferential and radial strain had poor diagnostic accuracy (AUC 0.644 and 0.541, respectively). Conclusion: Cardiac magnetic resonance LA ResS, LAAi, and LAVi have the highest diagnostic accuracy to identify HFpEF patients from non-HFpEF patients amongst clinically suspected HFpEF patients. Cardiac magnetic resonance feature tracking LV/RV parameters and tagging had low diagnostic accuracy to diagnose HFpEF.

Plasma apixaban levels in Chinese patients with chronic kidney disease-Relationship with renal function and bleeding complications.

Introduction: Accumulation of apixaban in plasma is a major concern in patients with chronic kidney disease (CKD). Studies that investigated plasma apixaban level in CKD patients and its association with clinically significant events are scarce. Methods: Patients with CKD Stage 1-4 who were taking apixaban, either 2.5 mg BD or 5 mg BD were recruited. The peak and trough plasma apixaban level were measured after 2 h and 12 h of last dose respectively. The results were correlated with renal function and clinical events during the period of follow-up from 1 January 2018 to 31 October 2021. Results: 141 patients (CKD Stage 1, n = 12; Stage 2, n = 74; Stage 3, n = 48, stage 4, n = 7) were included for analysis. The plasma peak and trough apixaban were significantly higher in patients with CKD stage 3 when compared with those having CKD stage 2 and 1 (peak levels: 223.4 ± 107.8 ng/ml vs. 161.0 ± 55.2 ng/ml vs. 126.6 ± 30.2 ng/ml; trough levels: 118.3 ± 67.9 ng/ml vs. 81.2 ± 33.0 ng/ml vs. 51.9 ± 31.1 ng/ml, p < 0.05 or all) in patients taking 5 mg BD. Plasma trough apixaban level was negatively correlated with eGFR in patients taking 5 mg BD (r 2 = -0.174, p < 0.001) and 2.5 mg BD (r 2 = -0.215, p < 0.05). The plasma peak and trough apixaban level correlated with PT (r 2 = 0.065, p = 0.003 and r 2 = 0.096, p < 0.01 respectively). Multivariate analysis showed that plasma trough apixaban levels were associated with the risk of bleeding complications (Odd ratio: 1.011, 95% CI:1.002-1.021, p = 0.023). Conclusion: The plasma apixaban level shows a trend of increase with worsening renal function, and an increase in the plasma apixaban level is suggestive of an increased risk of bleeding complications in patients with CKD. Further large-scale prospective studies are needed to evaluate relationship between plasma apixaban level and renal function as well as safety outcome in CKD patients. Moreover, the role of drug level monitoring should be prospectively evaluated for dosage optimization and the minimization of bleeding risks in CKD patients.

Isogenic Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes Reveal Activation of Wnt Signaling Pathways Underlying Intrinsic Cardiac Abnormalities in Rett Syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheless, the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either MeCP2wildtype or MeCP2mutant allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with MeCP2wildtype and control iPSC-CMs, MeCP2mutant iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various Wnt family genes in MeCP2mutant iPSC-CMs. Treatment of MeCP2mutant iPSC-CMs with a Wnt inhibitor XAV939 significantly decreased the ß-catenin protein level and CACN1AC expression and ameliorated their abnormal electrophysiological properties. In summary, our data provide novel insight into the contribution of activation of the Wnt/ß-catenin signaling cascade to the cardiac abnormalities associated with MeCP2 mutations in RTT.

Incidence, Prediction, and Outcomes of Major Bleeding After Percutaneous Coronary Intervention in Chinese Patients.

Background: The patterns of late major bleeding (MB) after percutaneous coronary intervention (PCI) remain unknown in Chinese patients. Objectives: This study sought to determine the incidence, prediction, and long-term outcomes of late MB in Chinese patients. Methods: This was a retrospective cohort study from 14 hospitals in Hong Kong. Participants were patients undergoing first-time PCI without MB within 30 days or death within 1 year. Patients were stratified by the presence of late MB, defined as MB between 30 and 365 days. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiac events (MACE). Results: A total of 32,057 patients were analyzed. After adjustment for baseline characteristics, periprocedural characteristics, and medications on discharge, the risks of all-cause mortality at 5 years were significantly higher with late MB (HR: 2.15; 95% CI: 1.92-2.41; P < 0.001). Late MB was also associated with a higher risk of MACE (HR: 1.57; 95% CI: 1.03-1.50; P < 0.001), myocardial infarction (HR: 1.25; 95% CI: 1.04-1.52; P = 0.02), and stroke (HR: 1.38; 95% CI: 1.09-1.73; P = 0.006). The CARDIAC (anti-Coagulation therapy, Age, Renal insufficiency, Drop In hemoglobin, baseline Anemia in Chinese patients) score had a good discriminating power for prediction of MB within 365 days (area under the receiver-operating characteristic curve: 0.76). Conclusions: Late MB was independently associated with a higher risk of mortality, MACE, myocardial infarction, and stroke in patients undergoing PCI. The CARDIAC score is a simple model that can predict MB after PCI. Prevention of MB represents an important strategy to optimize cardiovascular outcomes for patients undergoing PCI.

Sensitivity of ventricular systolic function to afterload during veno-arterial extracorporeal membrane oxygenation.

AIMS: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V-A ECMO during the acute and delayed stages of acute myocardial dysfunction. METHODS AND RESULTS: A total of 46 adult patients who were supported by peripheral V-A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V-A ECMO initiation (n = 45, 'acute phase') and mean day 4 ± 2 of V-A ECMO initiation (n = 36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from -6.1 (-8.9 to -4.0)% during 120% TBF to -8.8 (-11.5 to -6.0)% during 50% TBF (P < 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8-100.0)% vs. 22.5 (14.9-43.8)%, P < 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1-56.8)% vs. 22.8 (9.2-42.2)%, P = 0.012] and LV outflow tract velocity-time integral [45.8 (18.6-58.7)% vs. 24.2 (12.6-34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully. CONCLUSIONS: We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V-A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart-ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V-A ECMO.

Protocol for Home-Based Solution for Remote Atrial Fibrillation Screening to Prevent Recurrence Stroke (HUA-TUO AF Trial): a randomised controlled trial.

INTRODUCTION: Current international guidelines recommend ECG monitoring after an ischaemic stroke to detect atrial fibrillation (AF) in order to prevent stroke recurrence. However, optimal strategies to detect AF and the downstream management to prevent stroke recurrence remain to be established. The objective of the study was to explore the use of long-term home-based ECG monitoring for AF detection and stroke prevention in patients with a history of stroke. METHODS AND ANALYSIS: This prospective, randomised, open-label trial with blinded endpoint adjudication aimed to evaluate the efficacy of long-term home-based ECG monitoring for AF detection and stroke prevention in a 24-month period. Patients aged >18 years with a history of ischaemic stroke will be stratified according to the time from the index ischaemic stroke: <1, 1-3 and >3 years and then randomised in 1:1 to (1) home-based AF screening and (2) control. The home-based AF screening system comprises (1) a handheld single-lead ECG recorder (Comfit Healthcare Devices, Hong Kong SAR, China) and (2) a patient-facing smartphone application specially designed for the study. Patients randomised to the home-based AF group will record a 30 s single-lead ECG using a specially designed handheld ECG device every morning or when symptomatic. All remotely obtained data will be automatically transmitted in real-time through the study smartphone application to a secured cloud hosting and analysed using an artificial intelligence-based diagnostic system. When a diagnosis of AF is made with the system, the patients will be called back for a formal cardiology consultation within 1 week. The primary endpoint is the time to first detection of AF at 24 months of follow-up. Secondary endpoints include recurrent stroke or transient ischaemic attack, initiation of long-term anticoagulation therapy, hospitalisation for heart failure, cardiovascular death and all-cause death. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of The University of Hong Kong, and Hong Kong West Cluster, Hospital Authority, Hong Kong SAR, China. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04523649.

Plasma Rivaroxaban Level in Patients With Early Stages of Chronic Kidney Disease-Relationships With Renal Function and Clinical Events.

Introduction Drug accumulation of rivaroxaban is a concern in patients with chronic kidney disease (CKD). Data regarding the plasma rivaroxaban levels in early CKD patients and its relationship with clinical events is lacking. Methods Early CKD patients (Stage 1-3) with atrial fibrillation who received rivaroxaban (15 or 20 mg daily) were recruited. Plasma rivaroxaban levels were measured at 2 hours (peak) and 24 hours (trough) after drug administration, and correlated with eGFR and clinically significant events during the follow-up period (1 January 2018 to 31 October 2021). Results Ninety-two patients were included (CKD stage 1 n=10, stage 2 n=53, stage 3 n=29). Plasma trough levels in patients with stage 3 CKD were significantly higher than those with stage 2 and 1 CKD (66.0±34.9 ng/ml vs. 35.7 ± 24.7 ng/ml vs. 34.7 ± 26.2 ng/ml, respectively, p=0.005), and showed inverse relationship with eGFR (r=0.391, p=0.001) in patients receiving 20 mg daily. The plasma trough rivaroxaban level correlated with PT and APTT (r = 0.650 and 0.44, respectively, p<0.001 for both). Plasma trough rivaroxaban level in those with bleeding were higher than those who did not (59.9 ± 35.6 ng/ml vs. 41.1 ± 29.2 ng/ml, p=0.011), and multivariate analysis suggested that plasma trough rivaroxaban level was associated with the rate of bleeding complications (OR: 1.020, 95% CI 1.002-1.038, p=0.028). Conclusion Plasma trough rivaroxaban levels correlated with renal function in early CKD patients, and its measurement may help dosage optimization in patients with renal impairment. Moreover, our data suggests that there may be an association between plasma trough rivaroxaban level and the rate of bleeding complication.

Thromboembolic events and hemorrhagic stroke after mRNA (BNT162b2) and inactivated (CoronaVac) covid-19 vaccination: A self-controlled case series study.

Background: This study aims to evaluate the association between thromboembolic events and hemorrhagic stroke following BNT162b2 and CoronaVac vaccination. Methods: Patients with incident thromboembolic events or hemorrhagic stroke within 28 days of covid-19 vaccination or SARS-CoV-2 positive test during 23 February to 30 September 2021 were included. The incidence per 100,000 covid-19 vaccine doses administered and SARS-CoV-2 test positive cases were estimated. A modified self-controlled case series (SCCS) analysis using the data from the Hong Kong territory-wide electronic health and vaccination records. Seasonal effect was adjusted by month. Findings: A total of 5,526,547 doses of BNT162b2 and 3,146,741 doses of CoronaVac were administered. A total of 334 and 402 thromboembolic events, and 57 and 49 hemorrhagic stroke cases occurred within 28 days after BNT162b2 and CoronaVac vaccination, respectively. The crude incidence of thromboembolic events and hemorrhagic stroke per 100,000 doses administered for both covid-19 vaccines were smaller than that per 100,000 SARS-CoV-2 test positive cases. The modified SCCS detected an increased risk of hemorrhagic stroke in BNT162b2 14-27 days after first dose with adjusted IRR of 2.53 (95% CI 1.48-4.34), and 0-13 days after second dose with adjusted IRR 2.69 (95% CI 1.54-4.69). No statistically significant risk was observed for thromboembolic events for both vaccines. Interpretation: We detected a possible safety signal for hemorrhagic stroke following BNT162b2 vaccination. The incidence of thromboembolic event or hemorrhagic stroke following vaccination is lower than that among SARS-CoV-2 test positive cases; therefore, vaccination against covid-19 remains an important public health intervention. Funding: This study was funded by a research grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (reference COVID19F01).

Association between BNT162b2 or CoronaVac COVID-19 vaccines and major adverse cardiovascular events among individuals with cardiovascular disease.

AIMS: Concern about the cardiovascular safety of coronavirus disease 2019 (COVID-19) vaccines among individuals with cardiovascular disease (CVD) may lead to vaccine hesitancy. We sought to assess the association between two COVID-19 vaccines, BNT162b2 and CoronaVac, and the risk of major adverse cardiovascular events (MACE) in individuals with established CVD. METHODS AND RESULTS: We identified individuals with a history of CVD before 23 February 2021 and a diagnosis of MACE between 23 February 2021 and 31 January 2022 in Hong Kong. MACE was defined as a composite of myocardial infarction, stroke, revascularization, and cardiovascular death. Electronic health records from the Hong Kong Hospital Authority were linked to vaccination records from the Department of Health. A self-controlled case-series method was used to evaluate the risk of MACE for 0-13 and 14-27 days after two doses of COVID-19 vaccine. We estimated incidence rate ratios (IRRs) to compare the risk of MACE between each risk period and the baseline period. A total of 229 235 individuals with CVD were identified, of which 1764 were vaccinated and had a diagnosis of MACE during the observation period (BNT162b2 = 662; CoronaVac = 1102). For BNT162b2, IRRs were 0.48 [95% confidence interval (CI) 0.23-1.02] for the first dose and 0.87 (95% CI 0.50-1.52) for the second dose during the 0-13 days risk period, 0.40 (95% CI 0.18-0.93) for the first dose and 1.13 (95% CI 0.70-1.84) for the second dose during the 14-27 days risk period. For CoronaVac, the IRRs were 0.43 (95% CI 0.24-0.75) for the first dose and, 0.73 (95% CI 0.46-1.16) for the second dose during the 0-13 days risk period, 0.54 (95% CI 0.33-0.90) for the first dose and 0.83 (95% CI 0.54-1.29) for the second dose during the 14-27 days risk period. Consistent results were found in subgroup analyses for different sexes, age groups and different underlying cardiovascular conditions. CONCLUSION: Our findings showed no evidence of an increased risk of MACE after vaccination with BNT162b2 or CoronaVac in patients with CVD. Future research is required to monitor the risk after the third dose of each vaccine.