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.

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.

Prognosis and treatment of atrial fibrillation in Asian cities: 1-year review of the Asia-Pacific Heart Rhythm Society Atrial Fibrillation Registry.

AIMS: The aim of this study is to describe the implementation of the current guidance for stroke prevention and treatment option in atrial fibrillation (AF) and to evaluate mortality and morbidity in relation to therapeutic decisions, including persistence with treatment at 1 year in Asia-Pacific regions. METHODS AND RESULTS: We recruited 4664 patients consecutive in- and outpatients with AF who presented to cardiologists in five countries under the Asia-Pacific Heart Rhythm Society (APHRS) in whom 1-year follow-up was completed for 4003 (65.5% male; mean age 68.5 years). Oral anticoagulant (OAC) use remained high, 77% at follow-up, including 17% prescribed a vitamin K antagonist (VKA) and 60% a non-VKA oral anticoagulant (NOAC). At 1-year follow-up, 93% and 88% remained on a VKA or NOAC, respectively. With good adherence to OAC therapy, 1-year mortality was only 2.7%. Most deaths were non-cardiovascular (72.3%) and the 1-year incidence of stroke/transient ischaemic events (TIA) was low (<1%). Hospital readmissions were common for non-cardiovascular cases and atrial tachyarrhythmias. On multivariate analysis, independent baseline predictors of mortality and/or stroke/TIA/peripheral embolism were age, previous heart failure for >12 months, and malignancy. Independent predictors of mortality were age, chronic obstructive pulmonary disease, malignancy, and diuretic use. AF as a primary presentation was predictive of lower mortality and/or stroke/TIA/peripheral embolism as well as mortality. CONCLUSION: In this 1-year analysis of the APHRS-AF registry, overall OAC use and persistence were high and were associated with low 1-year cardiovascular mortality and morbidity, but mortality and morbidity related to non-cardiovascular causes were high in AF patients, particularly from malignancy and pneumonia.

Antithrombotic therapy and the risk of new-onset dementia in elderly patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of dementia. Little is known about the relationship of antithrombotic therapy and the risk of dementia in patients with AF without clinical stroke. METHOD: This was an observational study based on a hospital AF registry. Patients aged 65-85 years at the time of AF diagnosis were identified via the computerised database of the clinical management system. Patients with prior stroke or known cognitive dysfunction were excluded. The primary outcome was newly diagnosed dementia during the follow-up period. RESULTS: 3284 patients (mean age 76.4±5.3 years, 51.6% male) were included for analysis. The mean CHA2DS2-VASc score was 3.94±1.44. 18.5% patients were prescribed warfarin, 39.8% were prescribed aspirin and 41.7% were prescribed no antithrombotic therapy. After a mean follow-up of 3.6 years, 71 patients (2.2%) developed dementia, giving rise to an incidence of 0.61%/year. The incidence of dementia were 1.04%/year, 0.69%/year and 0.14%/year for patients on no therapy, aspirin and warfarin, respectively. Both univariate and multivariate analyses showed that age ≥75 years, female gender and high CHA2DS2-VASc score were associated with significantly higher risk of dementia; warfarin use was associated with significantly lower risk of dementia (HR: 0.14%, 95% CI 0.05 to 0.36, p<0.001). Patients on warfarin with time in therapeutic range (TTR) ≥65% had a non-significant trend towards a lower risk of dementia compared with those with TTR <65%. CONCLUSION: In elderly AF patients, warfarin therapy was associated with a significantly lower risk of new-onset dementia compared those with no therapy or aspirin.

Body volume is the major determinant of worsening renal function in acutely decompensated heart failure with reduced left ventricular ejection fraction.

AIMS: Little is known about the relative importance of body volume and haemodynamic parameters in the development of worsening of renal function in acutely decompensated heart failure (ADHF). To study the relationship between haemodynamic parameters, body water content and worsening of renal function in patients with heart failure with reduced ejection fraction (HFrEF) hospitalised for ADHF. METHODS AND RESULTS: This prospective observational study involved 51 consecutive patients with HFrEF (age: 73±14 years, male: 60%, left ventricular ejection fraction: 33.3%±9.9%) hospitalised for ADHF. Echocardiographic-determined haemodynamic parameters and body volume determined using a bioelectric impedance analyser were serially obtained. All patients received intravenous furosemide 160 mg/day for 3 days. There was a mean weight loss of 3.95±2.82 kg (p<0.01), and brain natriuretic peptide (BNP) reduced from 1380±901 pg/mL to 797±738 pg/mL (p<0.01). Nonetheless serum creatinine (SCr) increased from 134±46 µmol/L to 151±53 µmol/L (p<0.01), and 35% of patients developed worsening of renal function. The change in SCr was positively correlated with age (r=0.34, p=0.017); and negatively with the ratio of extracellular water to total body water, a parameter of body volume status (r=-0.58, p<0.001); E:E' ratio (r=-0.36, p=0.01); right ventricular systolic pressure (r=-0.40, p=0.009); and BNP (r=-0.40, p=0.004). Counterintuitively, no correlation was observed between SCr and cardiac output, or total peripheral vascular resistance. Regression analysis revealed that normal body volume and lower BNP independently predicted worsening of renal function. CONCLUSIONS: Normal body volume and lower serum BNP on admission were associated with worsening of renal function in patients with HFrEF hospitalised for ADHF.

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.

Importance of attributes and willingness to pay for oral anticoagulant therapy in patients with atrial fibrillation in China: A discrete choice experiment.

BACKGROUND: Adherence to oral anticoagulant therapy in patients with atrial fibrillation (AF) in China is low. Patient preference, one of the main reasons for discontinuation of oral anticoagulant therapy, is an unfamiliar concept in China. METHODS AND FINDINGS: A discrete choice experiment (DCE) was conducted to quantify patient preference on 7 attributes of oral anticoagulant therapy: antidote (yes/no), food-drug interaction (yes/no), frequency of blood monitoring (no need, every 6/3/1 month[s]), risk of nonfatal major bleeding (0.7/3.1/5.5/7.8[%]), risk of nonfatal stroke (ischemic/hemorrhagic) or systemic embolism (0.6/3.2/5.8/8.4[%]), risk of nonfatal acute myocardial infarction (AMI) (0.2/1.0/1.8/2.5[%]), and monthly out-of-pocket cost (0/120/240/360 RMB) (0 to 56 USD). A total of 16 scenarios were generated by using D-Efficient design and were randomly divided into 2 blocks. Eligible patients were recruited and interviewed from outpatient and inpatient settings of 2 public hospitals in Beijing and Shenzhen, respectively. Patients were presented with 8 scenarios and asked to select 1 of 3 options: 2 unlabeled hypothetical treatments and 1 opt-out option. Mixed logit regression model was used for estimating patients' preferences of attributes of oral anticoagulants and willingness to pay (WTP) with adjustments for age, sex, education level, income level, city, self-evaluated health score, histories of cardiovascular disease/other vascular disease/any stroke/any bleeding, and use of anticoagulant/antiplatelet therapy. A total of 506 patients were recruited between May 2018 and December 2019 (mean age 70.3 years, 42.1% women). Patients were mainly concerned about the risks of AMI (ß: -1.03; 95% CI: -1.31, -0.75; p < 0.001), stroke or systemic embolism (ß: -0.81; 95% CI: -0.90, -0.73; p < 0.001), and major bleeding (ß: -0.69; 95% CI: -0.78, -0.60; p < 0.001) and were willing to pay more, from up to 798 RMB to 536 RMB (124 to 83 USD) monthly. The least concerning attribute was frequency of blood monitoring (ß: -0.31; 95% CI: -0.39, -0.24; p < 0.001). Patients had more concerns about food-drug interactions even exceeding preferences on the 3 risks, if they had a history of stroke or bleeding (ß: -2.47; 95% CI: -3.92, -1.02; p < 0.001), recruited from Beijing (ß: -1.82; 95% CI: -2.56, -1.07; p < 0.001), or men (ß: -0.96; 95% CI: -1.36, -0.56; p < 0.001). Patients with lower educational attainment or lower income weighted all attributes lower, and their WTP for incremental efficacy and safety was minimal. Since the patients were recruited from 2 major hospitals from developed cities in China, further studies with better representative samples would be needed. CONCLUSIONS: Patients with AF in China were mainly concerned about the safety and effectiveness of oral anticoagulant therapy. The preference weighting on food-drug interaction varied widely. Patients with lower educational attainment or income levels and less experience of bleeding or stroke had more reservations about paying for oral anticoagulant therapies with superior efficacy, safety, and convenience of use.

Impact of coronavirus disease 2019 (COVID-19) outbreak on outcome of myocardial infarction in Hong Kong, China.

OBJECTIVE: To determine whether COVID-19 may adversely affect outcome of myocardial infarction (MI) patients in Hong Kong, China. BACKGROUND: The COVID-19 pandemic has infected thousands of people and placed enormous stress on healthcare system. Apart from being an infectious disease, it may affect human behavior and healthcare resource allocation which potentially cause treatment delay in MI. METHODS: This was a single center cross-sectional observational study. From November 1, 2019 to March 31, 2020, we compared outcome of patients admitted for acute ST-elevation MI (STEMI) and non-ST elevation MI (NSTEMI) before (group 1) and after (group 2) January 25, 2020 which was the date when Hong Kong hospitals launched emergency response measures to combat COVID-19. RESULTS: There was a reduction in daily emergency room attendance since January 25, 2020 (group 1,327/day vs. group 2,231/day) and 149 patients with diagnosis of MI were included into analysis (group 1 N = 85 vs. group 2 N = 64). For STEMI, patients in group 2 tended to have longer symptom-to-first medical contact time and more presented out of revascularization window (group 1 27.8 vs. group 2 33%). The primary composite outcome of in-hospital death, cardiogenic shock, sustained ventricular tachycardia or fibrillation (VT/VF) and use of mechanical circulatory support (MCS) was significantly worse in group 2 (14.1 vs. 29.7%, p = .02). CONCLUSIONS: More MI patients during COVID-19 outbreak had complicated in-hospital course and worse outcomes. Besides direct infectious complications, cardiology community has to acknowledge the indirect effect of communicable disease on our patients and system of care.

Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects　- A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial.

BACKGROUND: There are concerns that Asian patients respond differently to some medications. This study evaluated the efficacy and safety of evolocumab among Asian vs. other subjects in the FOURIER trial, which randomized stable atherosclerosis patients to receive either evolocumab or placebo.Methods and Results:Effects of adding evolocumab vs. placebo to background statin therapy on low-density lipoprotein cholesterol (LDL-C) reductions, cardiovascular outcomes, and adverse events were compared among 27,564 participants with atherosclerotic disease, according to self-reported Asian (n=2,723) vs. other (n=24,841) races followed for a median of 2.2 years in the FOURIER trial. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. At randomization, Asians had slightly lower LDL-C (median 89 [IQR 78-104] mg/dL vs. 92 [80-109] mg/dL; P<0.001) and were much less likely to be on a high-intensity statin (33.3% vs. 73.3%; P<0.001). Evolocumab lowered LDL-C more in Asians than in others (66% vs. 58%; P<0.001). The effect of evolocumab on the primary endpoint was similar in Asians (HR, 0.79; 95% CI, 0.61-1.03) and others (HR, 0.86; 95% CI, 0.79-0.93; P interaction=0.55). There was no excess of serious adverse events with evolocumab among Asians over others. CONCLUSIONS: Use of evolocumab robustly lowers LDL-C and is equally efficacious in lowering the risk of cardiovascular events and safe in Asians as it is in others.

Cardiac implantable electronic device surgery with interruption of warfarin forgoing post-operative bridging therapy in patients with moderate or high thromboembolic risks.

BACKGROUND: For patients taking warfarin and undergoing pacemaker or implantable cardioverter-defibrillator surgery, clinical evidence and guidelines support continuation of warfarin therapy, as opposed to interruption of warfarin therapy with heparin bridging. Interruption of warfarin without post-operative bridging therapy may be a feasible alternative but data is sparse. METHODS: This is a single-arm observational study including adults who had interruption of warfarin therapy without post-operative bridging therapy for cardiac implantable electronic device (CIED) surgery performed between 2010 and 2019 in a tertiary referral hospital. The primary outcome was a composite of all-cause mortality, arterial or venous thromboembolic events. The secondary outcomes were clinically significant device-pocket hematoma and other procedural complications. RESULTS: Of the 411 patients analysed including 257 patients (62.5%) who had mechanical heart valves, the primary outcome developed in 5 (1.2%) patients within 30 days after surgery, including death in 3 (0.7%) patients, transient ischemic attack in 1 (0.2%) patient and non-CNS embolism in 1 (0.2%) patient. Clinically significant hematomas occurred in 24 (5.8%) patients, including 15 (3.7%) requiring additional interruption of anti-coagulation and 6 (1.5%) requiring clot evacuation. Other procedural complications and bleeding events were rare (< 1%). CONCLUSIONS: Warfarin interruption without post-operative bridging therapy for CIED surgery was associated with low thromboembolic risks and acceptable bleeding risk. Randomized controlled trials are required to formulate an optimal approach to anti-coagulation management.

The impact of cigarette smoking in predicting stroke using CHADS2 and CHA2DS2-VASc schemas.

OBJECTIVE: To determine the impact of smoking status in the prediction of stroke using CHADS2 and CHA2DS2-VASc schemes. METHODS: Five hundred twenty-eight consecutive patients with arrhythmic symptoms and without any documented arrhythmia from Queen Mary Hospital, Hong Kong, were followed up to determine the incidence of ischemic stroke, new-onset atrial fibrillation (AF), or all-cause mortality. Smoking status was classified into nonsmokers and smokers. The pairwise comparisons of C-statistics for outcomes were performed. RESULTS: During a median follow-up period of 6.2 years, 65 (12.3%) individuals developed ischemic stroke. Smokers experienced higher annual incidence of stroke, a new-onset AF, and all-cause death compare to nonsmokers, with corresponding hazard ratio (HR) of stroke, AF, and all-cause death being 2.51 (95% confidence intervals, CI 1.36als, CIse death bein 1.15a3.24), and 1.95 (95% CI 1.161.95 (95% CIath being 2.51 (95% confidence corr2 and CHA2DS2-VASc for stroke were 0.60 (95% CI 0.51 for stp = 0.09) and 0.59 (95% CI 0.50 (95%, p = 0.15) respectively, whereas the C-statistics of CHADS2 and CHA2DS2-VASc were 0.66 (95% CI 0.61 were 0p = 0.005), 0.75 (95% CI 0.7 CI 0.7p < 0.0001), respectively among nonsmokers. After incorporating smoking, both the CHADS2-smoking and CHA2DS2-VASc-smoking achieved better C-statistics for new-onset ischemic stroke prediction superior to baseline score systems in male groups. CONCLUSION: Cigarette smoking status has impact on stroke stratification using CHADS2 and CHA2DS2-VASc scheme. The discrimination of the CHADS2 and CHA2DS2-VASc scheme for stroke can be significantly improved if smoking status is additionally considered.

Point-of-care ultrasound augments physical examination learning by undergraduate medical students.

BACKGROUND: Little is known about the impact of the provision of handheld point-of-care ultrasound (POCUS) devices on physical examination skills of medical students. METHODS: We describe an educational initiative that comprised a POCUS workshop followed by allocation of a POCUS device to medical students for use over the subsequent 8 weeks. They were encouraged to scan patients and correlate their physical examination findings. A mobile instant messaging group discussion platform was set to provide feedback from instructors. Physical examination skills were assessed by means of clinical examination. RESULTS: 210 final-year medical students from the University of Hong Kong participated in the programme. 46.3% completed the end of programme electronic survey: 74.6% enjoyed using the POCUS device, 50.0% found POCUS useful to validate physical examination findings and 47.7% agreed that POCUS increased their confidence with physical examination. 93.9% agreed that the programme should be incorporated into the medical curriculum and 81.9% would prefer keeping the device for longer time from 16 weeks (45.6%) to over 49 weeks (35.3%). Medical students who participated in the POCUS programme had a higher mean score for abdominal examination compared with those from the previous academic year with no POCUS programme (3.65±0.52 vs 3.21±0.80, p=0.014), but there was no statistically significant difference in their mean score for cardiovascular examination (3.62±0.64 vs 3.36±0.93, p=0.203). CONCLUSION: The POCUS programme that included provision of a personal handheld POCUS device improved students' attitude, confidence and ability to perform a physical examination.

Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND: It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF). OBJECTIVE: To compare the risk for osteoporotic fracture between anticoagulants. DESIGN: Population-based cohort study. SETTING: Territory-wide electronic health record database of the Hong Kong Hospital Authority. PARTICIPANTS: Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018. MEASUREMENTS: Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score-weighted cumulative incidence differences (CIDs). RESULTS: There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, -0.88% [95% CI, -1.66% to -0.21%]; dabigatran CID, -0.81% [CI, -1.34% to -0.23%]; and rivaroxaban CID, -1.13% [CI, -1.67% to -0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, -0.06% [CI, -0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, -0.32% [CI, -0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, -0.25% [CI, -0.86% to 0.40%]). LIMITATION: Residual confounding is possible. CONCLUSION: Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit-risk assessment when choosing between anticoagulants. PRIMARY FUNDING SOURCE: The University of Hong Kong and University College London Strategic Partnership Fund.

Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Platform to Study SARS-CoV-2 Related Myocardial Injury.

BACKGROUND: SARS-CoV-2 infection is associated with myocardial injury, but there is a paucity of experimental platforms for the condition.Methods and Results:Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected by SARS-CoV-2 for 3 days ceased beating and exhibited cytopathogenic changes with reduced viability. Active viral replication was evidenced by an increase in supernatant SARS-CoV-2 and the presence of SARS-CoV-2 nucleocaspid protein within hiPSC-CMs. Expressions of BNP, CXCL1, CXCL2, IL-6, IL-8 and TNF-α were upregulated, while ACE2 was downregulated. CONCLUSIONS: Our hiPSC-CM-based in-vitro SARS-CoV-2 myocarditis model recapitulated the cytopathogenic effects and cytokine/chemokine response. It could be exploited as a drug screening platform.

Understanding the barriers to using oral anticoagulants among long-term aspirin users with atrial fibrillation - a qualitative study.

BACKGROUND: Despite international treatment guidelines currently advocating oral anticoagulants (OACs) as the only appropriate stroke prevention therapy for patients with atrial fibrillation (AF) and evidence that OACs can greatly reduce the risk of stroke with similar risk of bleeding compared with aspirin, the underuse of OACs in patients with AF is common globally, especially in Asia. This study aimed to identify the barriers to prescribing and using OACs among long-term aspirin users with AF. METHOD: Face-to-face interviews were conducted with fourteen eligible patients with AF using a semi-structured interview guide. The interview recordings were transcribed verbatim and data was analyzed according to the principles of thematic analysis. RESULTS: Five themes were developed: awareness of AF symptoms and diagnosis; knowledge and understanding of AF and stroke prevention therapy; role of decision-making in prescribing; willingness to switch from aspirin to OACs; and impact of OAC regimen on daily living. The majority of the patients were not aware of the symptoms and diagnosis of AF and only had a vague understanding of the illness and stroke prevention therapy, leading to their minimal involvement in decisions relating to their treatment. Some patients and their caregivers were particularly concerned about the bleeding complications from OACs and perceived aspirin to be a suitable alternative as they find the adverse effects from aspirin manageable and so preferred to remain on aspirin if switching to OACs was not compulsory. Lastly, the lifestyle modifications required when using warfarin, e.g. alternative dosing regimen, diet restriction, were seen as barriers to some patients and caregivers. CONCLUSION: The findings revealed patients' knowledge gap in AF management which may be targeted using educational interventions to improve patients' understanding of AF and its management and hence encourage active participation in the decision-making of their treatment in the future.

Incidence of dual antiplatelet therapy interruption within 1 year after primary percutaneous coronary intervention in patients with acute ST elevation myocardial infarction.

BACKGROUND: After primary percutaneous coronary intervention (PPCI) in patients with acute ST elevation myocardial infarction (STEMI), dual antiplatelet therapy (DAPT) is recommended to continue for 1 year. Occasionally, DAPT interruption may be required due to bleeding issues or unplanned surgical procedures. OBJECTIVE: To systematically evaluate the incidence of DAPT interruption within 1 year after PPCI. METHODS AND RESULTS: This was a single-centre, retrospective registry study. Consecutive patients with STEMI who underwent PPCI from 2013 to 2017 (N=538) were recruited into the analysis. The primary outcome was the incidence of interruption of DAPT within 1 year from the index PPCI. Secondary outcomes included incidence of bleeding in 1 year and prevalence of high bleeding risk (HBR) criteria at index presentation. Within 1 year, 17.1% (84/490) of post-PPCI survivors needed DAPT interruption and 7.1% (35/490) had major bleeding (Bleeding Academic Research Consortium type 3 or 5). At index presentation, HBR criteria were present in 36.1% (194/538) of patients. On univariate analysis, age, female gender, anaemia, anticoagulation, diabetes, hypertension and being a non-smoker were associated with DAPT interruption. On multivariate analysis, age was the only independent factor to predict DAPT interruption. CONCLUSION: DAPT interruption was not uncommon after PPCI in patients with STEMI particularly in the elderly. This has implication on stent selection during PPCI, and further studies are required to investigate which type of stent may best suit our real-life patients with STEMI.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention of Recurrent Cardiovascular Events in a Real-World Cohort of Post-Acute Myocardial Infarction Patients.

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

Prognostic implications of statin intolerance in stable coronary artery disease patients with different levels of high-sensitive troponin.

BACKGROUND: The prognostic implication of statin in tolerance (SI) in those with stable CAD remains unclear. We hypothesized that SI is of higher prognostic significance in stable CAD patients with elevated high-sensitive cardiac troponin I (hs-cTnI). METHODS: A total of 952 stable CAD patients from the prospective Hong Kong CAD study who had complete clinical data, biomarker measurements and who were prescribed statin therapy were studied. RESULTS: We identified 13 (1.4%) and 125 (13.1%) patients with complete and partial SI, respectively. At baseline, patients with SI were more likely to have diabetes mellitus and a higher hs-cTnI level, but no difference in LDL-C level compared with those without SI. After 51 months of follow-up, patients with SI had a higher mean LDL-C level than those without SI. A total of 148 (15.5%) patients developed major adverse cardiovascular events (MACEs). Both SI (HR 1.52, 95% CI 1.06-2.19, P = 0.02) and elevated hs-cTnI (HR 3.18, 95% CI 2.07-4.89, P < 0.01) were independent predictors of a MACE in patients with stable CAD. When stratified by hs-cTnI level, SI independently predicted MACE-free survival only in those with elevated hs-cTnI (HR 1.51, 95% CI 1.01-2.24, P = 0.04). CONCLUSIONS: SI independently predicted MACE in patients with stable CAD and high hs-cTnI, but not in those with low hs-cTnI. Hs-cTnI may be used to stratify stable CAD patients who have SI for intensive lipid-lowering therapy using non-statin agents.

TIMI risk score for secondary prevention of recurrent cardiovascular events in a real-world cohort of post-non-ST-elevation myocardial infarction patients.

BACKGROUND: Patients who survive non-ST-elevation myocardial infarction (NSTEMI) are at heightened risk of recurrent cardiovascular events. Data on long-term secondary atherothrombotic risk stratification are limited. OBJECTIVES: To stratify post-NSTEMI patients for risk of recurrent cardiovascular events to maximise benefit from aggressive secondary prevention strategies using the TIMI Risk Score for Secondary Prevention (TRS 2°P) score in a real-world cohort of NSTEMI patients. METHODS AND RESULTS: This was a single-centre observational study of 891 post-NSTEMI patients (73.7 ± 12.7 years; male: 54.2%). The TRS 2°P is a nine-point risk stratification tool to predict cardiovascular events in patients with established cardiovascular disease. The primary outcome was a composite endpoint of cardiovascular death, non-fatal MI and non-fatal ischaemic stroke. After a median follow-up of 31 months (IQR: 11.4 - 60.2), 281 patients (31.5%) had developed a primary outcome (13.3%/year) including 196 cardiovascular deaths, 94 non-fatal MIs and 22 non-fatal strokes. The TRS 2°P score was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P score =0 was 1.6%, and increased progressively to 47.4% for those with a TRS 2°P score ≥6 (HR: 20.18, 95% CI: 4.85 to 84.05, p<0.001). Similar associations were also observed between the TRS 2°P score and cardiovascular death and MI (fatal and non-fatal), but not non-fatal ischaemic stroke. CONCLUSION: The TRS 2°P score stratified post-NSTEMI patients for risk of future cardiovascular events and potentially help guide the selection of more aggressive secondary prevention therapy.