Comparison of dual-bolus versus dual-sequence techniques for determining myocardial blood flow and myocardial perfusion reserve by cardiac magnetic resonance stress perfusion: From the Automated Quantitative analysis of myocardial perfusion cardiac Magnetic Resonance Consortium.

BACKGROUND: Quantitative stress cardiac magnetic resonance (CMR) can be performed using the dual-sequence (DS) technique or dual-bolus (DB) method. It is unknown if DS and DB produce similar results for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). The study objective is to investigate if there are any differences between DB- and DS-derived MBF and MPR. METHODS: Retrospective observational study with 168 patients who underwent stress CMR. DB and DS methods were simultaneously performed on each patient on the same day. Global and segmental stress MBF and rest MBF values were collected. RESULTS: Using Bland-Altman analysis, segmental and global stress MBF values were higher in DB than DS (0.22 ± 0.60 mL/g/min, p < 0.001 and 0.20 ± 0.48 mL/g/min, p = 0.005, respectively) with strong correlation (r = 0.81, p < 0.001 for segmental and r = 0.82, p < 0.001 for global). In rest MBF, segmental and global DB values were higher than by DS (0.15 ± 0.51 mL/g/min, p < 0.001 and 0.14 ± 0.36 mL/g/min, p = 0.011, respectively) with strong correlation (r = 0.81, p < 0.001 and r = 0.77, p < 0.001). Mean difference between MPR by DB and DS was -0.02 ± 0.68 mL/g/min (p = 0.758) for segmental values and -0.01 ± 0.49 mL/g/min (p = 0.773) for global values. MPR values correlated strongly as well in both segmental and global, both (r = 0.74, p < 0.001) and (r = 0.75, p < 0.001), respectively. CONCLUSION: There is a very good correlation between DB- and DS-derived MBF and MPR values. However, there are significant differences between DB- and DS-derived global stress and rest MBF. While MPR values did not show statistically significant differences between DB and DS methods.

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.

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.

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.

Modelling the impact of travel restrictions on COVID-19 cases in Hong Kong in early 2020.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease. OBJECTIVE: To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019. METHODS: We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The R0 was obtained from previous clinical studies. RESULTS: Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary, apart from having complete border closure. CONCLUSIONS: Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local R0 to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities.

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.

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.

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.

Impact of provision of time in therapeutic range value on anticoagulation management in atrial fibrillation patients on warfarin.

INTRODUCTION: The importance of time in therapeutic range (TTR) in patients prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF) cannot be overemphasised. AIM: To evaluate the impact of provision of TTR results during clinic visits on anticoagulation management. DESIGN: Single-centred, randomised controlled study. SETTING: Fifteen arrhythmia clinics in Hong Kong. PATIENTS: AF patients prescribed warfarin. INTERVENTIONS: Provision of TTR or no provision of TTR. MAIN OUTCOME MEASURES: A documented discussion between doctors and patients about switching warfarin to a non-vitamin K oral anticoagulant (NOAC). RESULTS: Four hundred and eighty one patients with AF prescribed warfarin were randomly assigned to (1) a TTR provision group or (2) control. Their mean age was 73.6±12.0 years and 60.7% were men. The mean CHA2DS2-VASc score was 3.2±1.6 and the mean HASBLED score was 1.7±1.2. The mean TTR was 63.9%±29.9%. At the index clinic visit, 71 of 481 patients (14.8%) had a documented discussion about switching warfarin to a NOAC. Patients with provision of TTR results were more likely to discuss switching warfarin to a NOAC than controls (19.1% vs 10.6%, P=0.03), especially those with a TTR <65% (35.2% vs 10.6%, P<0.001). A higher proportion of patients with provision of TTR results switched to a NOAC (5.9% vs 4.1%, P=0.49). CONCLUSIONS: The provision of TTR among patients on warfarin was associated with a discussion about switching from warfarin to a NOAC in those with TTR <65%, but did not result in actual switching to a NOAC, suggesting additional barriers.

The Pathogenic Mechanisms of and Novel Therapies for Lamin A/C-Related Dilated Cardiomyopathy Based on Patient-Specific Pluripotent Stem Cell Platforms and Animal Models.

Variants (pathogenic) of the LMNA gene are a common cause of familial dilated cardiomyopathy (DCM), which is characterised by early-onset atrioventricular (AV) block, atrial fibrillation and ventricular tachyarrhythmias (VTs), and progressive heart failure. The unstable internal nuclear lamina observed in LMNA-related DCM is a consequence of the disassembly of lamins A and C. This suggests that LMNA variants produce truncated or alternative forms of protein that alter the nuclear structure and the signalling pathway related to cardiac muscle diseases. To date, the pathogenic mechanisms and phenotypes of LMNA-related DCM have been studied using different platforms, such as patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) and transgenic mice. In this review, point variants in the LMNA gene that cause autosomal dominantly inherited forms of LMNA-related DCM are summarised. In addition, potential therapeutic targets based on preclinical studies of LMNA variants using transgenic mice and human iPSC-CMs are discussed. They include mitochondria deficiency, variants in nuclear deformation, chromatin remodelling, altered platelet-derived growth factor and ERK1/2-related pathways, and abnormal calcium handling.

Cardiovascular outcomes following hospitalisation for exacerbation of bronchiectasis: a territory-wide study.

BACKGROUND: Although bronchiectasis is reported to be associated with cardiovascular disease, evidence for an association with cardiovascular events (CVEs) is lacking. METHODS: A territory-wide retrospective cohort study was conducted in Hong Kong involving all patients who had bronchiectasis diagnosed in public hospitals and clinics between 1 January 1993 and 31 December 2017 were included. Patients were allocated to be exacerbator or non-exacerbator group based on hospitalzied bronchiecsis history and CVEs over the next 5 years determined. Propensity score matching was used to balance baseline characteristics. RESULTS: 10 714 bronchiectasis patients (mean age 69.6±14.4 years, 38.9% men), including 1230 in exacerbator group and 9484 in non-exacerbator group, were analysed. At 5 years, 113 (9.2%) subjects in the exacerbator group and 87 (7.1%) in the non-exacerbator group developed composite CVEs. After adjustment for age, sex, smoking and risk factors for cardiovascular disease, bronchiectasis exacerbation was associated with increased risks for acute myocardial infarction (AMI), congestive heart failure (CHF) and CVE compared with those in the non-exacerbator group with adjusted HR of 1.602 (95% CI 1.006-2.552, p value=0.047), 1.371 (95% CI 1.016-1.851, p value=0.039) and 1.238 (95% CI 1.001-1.532, p=0.049) in the whole cohort. Findings were similar for the propensity score-matched cohort for AMI and CVE. CONCLUSION: Patients who were hospitalised for exacerbation of bronchiectasis were at significantly increased risk of AMI, CHF and CVE over a 5-year follow-up period.

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.

Aromatase Inhibitor Therapy Increases the Risk of New-Onset Atrial Fibrillation in Patients With Breast Cancer.

Background: Previous studies suggest that aromatase inhibitors (AIs) increase the risk of adverse cardiovascular events and cardiac arrhythmias in patients with breast cancer, but it is unclear whether AIs also increase the risk of new-onset atrial fibrillation (AF). Objectives: The purpose of this study was to investigate whether the use of AIs was associated with an increased risk of new-onset AF in patients with breast cancer. Methods: We performed a retrospective analysis involving 5,707 patients with breast cancer (mean age 63.9 ± 11.2 years and 99.9% women) who received adjunctive hormone therapy with an AI (AI group, n = 4,878) or tamoxifen (tamoxifen group, n = 829) in Hong Kong between January 1, 1999, and December 31, 2020. After propensity score matching, there were 1,658 and 829 patients with balanced characteristics in the AI group and tamoxifen group, respectively. Results: After 8,863 patient-years of follow-up, patients who were prescribed AI had a trend toward more new-onset arrhythmias compared with those prescribed tamoxifen (0.62 vs 0.30 per 100 patient-years; crude HR: 2.05; P = 0.053). The difference in arrhythmic risk was mainly driven by a higher incidence rate of new-onset AF in the AI group (0.59 vs 0.27 per 100 patient-years; crude HR: 2.18; P = 0.046). The use of AIs was confirmed to be an independent risk factor for new-onset AF on multivariate analysis (adjusted HR: 2.75; P = 0.01). Conclusions: Among breast cancer patients prescribed adjunctive hormonal therapy, AI was associated with an increased risk of new-onset AF. Regular surveillance for new-onset AF should be considered in breast cancer patients treated with an AI.

The traditional Chinese medicine Qiliqiangxin in heart failure with reduced ejection fraction: a randomized, double-blind, placebo-controlled trial.

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .

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.

Immunopathogenesis of Immune Checkpoint Inhibitor Induced Myocarditis: Insights from Experimental Models and Treatment Implications.

Despite the extraordinary success of immune checkpoint inhibitors (ICIs) in cancer treatment, their use is associated with a high incidence of immune-related adverse events (IRAEs), resulting from therapy-related autoimmunity against various target organs. ICI-induced myocarditis is one of the most severe forms of IRAE, which is associated with risk of hemodynamic compromise and mortality. Despite increasing recognition and prompt treatment by clinicians, there remain significant gaps in knowledge regarding the pathophysiology, diagnosis and treatment of ICI-induced myocarditis. As the newly emerged disease entity is relatively rare, it is challenging for researchers to perform studies involving patients at scale. Alternatively, mouse models have been developed to facilitate research understanding of the pathogenesis of ICI-induced myocarditis and drug discovery. Transgenic mice with immune checkpoint genes knocked out allow induction of myocarditis in a highly reproducible manner. On the other hand, it has not been possible to induce ICI-induced myocarditis in wild type mice by injecting ICIs monotherapy alone. Additional interventions such as combinational ICI, tumor inoculation, cardiac sarcomere immunization, or cardiac irradiation are necessary to mimic the underlying pathophysiology in human cancer patients and to induce ICI-induced myocarditis successfully. This review focuses on the immunopathogenesis of ICI-induced myocarditis, drawing insights from human studies and animal models, and discusses the potential implications for treatment.