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Abstract Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24–2.17, p

Abstract Aims Rhythm control therapy has shown great benefits for patients with atrial fibrillation (AF) and heart failure (HF). However, few studies have evaluated the effects of rhythm control on left ventricular ejection fraction (LVEF) trajectory across the whole HF spectrum. Our study explored the prevalence and predictors of LVEF trajectory changes and their prognostic implications following rhythm control. Methods and results Depending on the treatment strategy, the cohort was classified into rhythm and rate control groups. Alterations in HF types and LVEF trajectory were recorded. The observational endpoints were all‐cause mortality and HF‐related admission. Predictors of LVEF trajectory improvement in the rhythm control group were evaluated. After matching, the two groups had similar age [mean age (years): rhythm/rate control: 63.96/65.13] and gender [male: rhythm/rate control: n = 228 (55.6%)/233 (56.8%)]. Based on baseline LVEF measurement, the post‐matched cohort had 490 HF with preserved ejection fraction (rhythm/rate control: n = 260/230; median LVEF: 58.00%/57.00%), 99 HF with mildly reduced ejection fraction (rhythm/rate control: n = 50/49; median LVEF: 45.00%/46.00%), and 231 HF with reduced ejection fraction (rhythm/rate control: n = 100/131; median LVEF: 32.50%/33.00%). Trajectory analysis found that the rhythm control group had a greater percentage of LVEF trajectory improvement than the rate control group [80 (53.3%) vs. 71 (39.4%), P = 0.012]. Cox regression analysis also showed that the rhythm control group was more likely to have improved LVEF trajectory compared with the rate control group {hazard ratio [HR] 1.671 [95% confidence interval (CI) 1.196–2.335], P = 0.003}. In the survival analysis, the rhythm control group experienced significant lower risks of all‐cause mortality [HR 0.600 (95% CI 0.366–0.983), P = 0.043] and HF‐related admission [HR 0.611 (95% CI 0.496–0.753), P

Summary: Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01).

Background and aims: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery and is associated with adverse clinical outcomes. Our study aimed at determining the clinical and echocardiographic predictors of POAF in patients with cardiac surgery and management of this group of patients may improve their outcome. Methods: We prospectively enrolled patients from the department of cardiovascular surgery in the Second Hospital of Tianjin Medical University from October 23, 2020 to October 30, 2022, without a history of atrial fibrillation. Cox regression was used to identify significant predictors of POAF. Results: A total of 217 patients (79 [36.41 %] were female, 63.96 ± 12.32 years) were included. 88 (40.55 %) patients met the criteria for POAF. Cox regression showed that preoperative left atrial diameter (LAD) (HR: 1.040, 95 % CI 1.008–1.073, p = 0.013) and postoperative QRS/LVEDD (HR: 0.398, 95 % CI 0.193–0.824, p = 0.013) and E/e’ (HR: 1.029, 95 % CI 1.002–1.057，p = 0.033) were predictors of POAF. Conclusion: Preoperative LAD and postoperative QRS/LVEDD and E/e’ were predictors of POAF in patients undergoing cardiac surgery. Trial registration site: http://www.chictr.org.cn Registration number: ChiCTR2200063344.

Abstract Background The association of longitudinal uric acid (UA) changes with cardiac conduction block risk is unclear. We aimed to identify the trajectories of UA and explore its association with cardiac conduction block. Methods A total of 67,095 participants with a mean age of 53.12 years were included from the Kailuan cohort in Tangshan, China, who were free of cardiac conduction block and with repeated measurements of UA from 2006 to 2012. UA trajectories during 2006 to 2012 were identified by group-based trajectory modeling. Cox proportional hazard regression models were used to assess the association of UA trajectories with cardiac conduction block. Results We categorized three observed discrete trajectories of UA during 2006–2012 period: low-stable, moderate-stable, and high-stable. Over a median follow-up of 6.19 years, we identified 1405 (2.09%) incident cardiac conduction block. Compared to those in the low-stable trajectory, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of cardiac conduction block in the moderate-stable and high-stable trajectory were 1.30 (1.16–1.47) and 1.86 (1.56–2.22), and HRs of atrioventricular block were 1.39 (1.12–1.72) and 2.90 (2.19–3.83), and HRs of bundle branch blocks were 1.27 (1.10–1.47) and 1.43 (1.13–1.79). Notably, although the average UA level in the moderate-stable UA trajectory group is within the normal range, the risk of cardiac conduction block has increased. Conclusions The moderate-stable and high-stable trajectories are associated with increased risk for new-onset cardiac conduction block. Monitoring UA trajectories may assist in identifying subpopulations at higher risk for cardiac conduction block.

Abstract Progressive cerebral infarction (PCI) is a common complication in patients with ischemic stroke that leads to poor prognosis. Blood pressure (BP) can indicate post‐stroke hemodynamic changes which play a key role in the development of PCI. The authors aim to investigate the association between BP‐derived hemodynamic parameters and PCI. Clinical data and BP recordings were collected from 80 patients with cerebral infarction, including 40 patients with PCI and 40 patients with non‐progressive cerebral infarction (NPCI). Hemodynamic parameters were calculated from the BP recordings of the first 7 days after admission, including systolic and diastolic BP, mean arterial pressure, and pulse pressure (PP), with the mean values of each group calculated and compared between daytime and nighttime, and between different days. Hemodynamic parameters and circadian BP rhythm patterns were compared between PCI and NPCI groups using t‐test or non‐parametric equivalent for continuous variables, Chi‐squared test or Fisher's exact test for categorical variables, Cox proportional hazards regression analysis and binary logistic regression analysis for potential risk factors. In PCI and NPCI groups, significant decrease of daytime systolic BP appeared on the second and sixth days, respectively. Systolic BP and fibrinogen at admission, daytime systolic BP of the first day, nighttime systolic BP of the third day, PP, and the ratio of abnormal BP circadian rhythms were all higher in the PCI group. PCI and NPCI groups were significantly different in BP circadian rhythm pattern. PCI is associated with higher systolic BP, PP and more abnormal circadian rhythms of BP.

Abstract Background Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune‐related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. Methods We conducted a multicenter retrospective study to characterize ICI‐associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer–Lemeshow test. Results Forty‐four patients were identified, including thirty‐five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin‐I (cTnI) levels (p

Abstract Background The accuracy of electrocardiogram (ECG) interpretation by doctors are affected by the available clinical information. However, having a complete set of clinical details before making a diagnosis is very difficult in the clinical setting especially in the early stages of the admission process. Therefore, we developed an artificial intelligence-assisted ECG diagnostic system (AI-ECG) using natural language processing to provide screened key clinical information during ECG interpretation. Methods Doctors with varying levels of training were asked to make diagnoses from 50 ECGs using a common ECG diagnosis system that does not contain clinical information. After a two-week-blanking period, the same set of ECGs was reinterpreted by the same doctors with AI-ECG containing clinical information. Two cardiologists independently provided diagnostic criteria for 50 ECGs, and discrepancies were resolved by consensus or, if necessary, by a third cardiologist. The accuracy of ECG interpretation was assessed, with each response scored as correct/partially correct = 1 or incorrect = 0. Results The mean accuracy of ECG interpretation was 30.2% and 36.2% with the common ECG system and AI-ECG system, respectively. Compared to the unaided ECG system, the accuracy of interpretation was significantly improved with the AI-ECG system (P for paired t-test = 0.002). For senior doctors, no improvement was found in ECG interpretation accuracy, while an AI-ECG system was associated with 27% higher mean scores (24.3 ± 9.4% vs. 30.9 ± 10.6%, P = 0.005) for junior doctors. Conclusion Intelligently screened key clinical information could improve the accuracy of ECG interpretation by doctors, especially for junior doctors.

Abstract Background This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Methods Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow‐up conducted until September 2021. Patients who had received medical castration for

Abstract Objective Patients treated with preoperative chemotherapy and immunotherapy for bladder cancer may be at increased risk of cardiotoxicity and electrophysiological abnormalities. This study aimed to analyze their electrocardiographic (ECG) alterations. Methods Patients with bladder cancer who were hospitalized and receiving tislelizumab plus nab‐paclitaxel (TnP) were enrolled prospectively. ECG, cardiac biomarkers, and echocardiography were performed at baseline and the end of TnP. Results A total of 60 patients (76.7% males), including 30 muscle‐invasive and 30 non‐muscle‐invasive bladder cancer, received three or four cycles of TnP, respectively. Hypertension was the commonest comorbidity (41.7%), and 25 patients (41.7%) were prescribed cardiovascular drugs. In comparison with baseline characteristics, cardiac troponin I (cTnI) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) were within normal ranges after TnP. However, echocardiographic parameter of left ventricular ejection fraction slightly decreased after TnP (62.81 ± 3.81% to 61.10 ± 4.37%, p = .011). The incidence of abnormal ECG increased from 65.0% at baseline to 76.7%, of which only a higher prevalence of fragmented QRS (fQRS) was observed (33.3% to 50.0%, p = .013; mainly in inferior leads). ECG parameters of QT dispersion (QTd) were prolonged significantly after the regimen (39.50 ± 11.37 to 44.20 ± 15.85 ms, p = .019). Conclusion In bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy, the main ECG abnormality was fQRS and QTd, with relatively normal cardiac biomarkers and echocardiographic parameters. Regular ECG screening should be carried out carefully to detect potential cardiotoxicity in the long‐term follow‐up.

Abstract Objective This population‐based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)‐related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). Methods Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa‐related mortality. Results Altogether, 4126 patients (median follow‐up 3.1[interquartile range 1.4–6.0] years) were included. A J‐shaped association was observed between baseline UA level and PCa‐related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above‐mean baseline UA levels (hazard ratio (HR) per standard deviation‐increase 1.35 [95% confidence interval 1.21,1.51], p

Abstract Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose‐dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin‐induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin‐induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro. Methods Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate‐buffered saline, doxorubicin, and doxorubicin with resveratrol). Results Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α‐smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels. Conclusion Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin‐induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

Background: The aim of this work was to investigate left atrial electrophysiological properties for their ability to predict the recurrence of atrial fibrillation (AF) following pulmonary vein isolation (PVI). Methods: The study comprised 53 patients with AF [62 (interquartile range (IQR): 52–68) years old; 47.2% females]. High-density, three-dimensional electro-anatomic mapping using PentaRay was conducted during sinus rhythm in the left atrium (LA) immediately after PVI. LA conduction time, conduction velocity in predefined anterior and posterior routes, low voltage area percentage and distribution were assessed. Results: The AF recurrence group had longer LA conduction time compared to the non-recurrence group [11 (IQR: 10–12) ms vs. 9 (IQR: 8–10) ms, p = 0.001). The percent low voltage area was greater in the recurrence group than the non-recurrence group [31.2 (IRQ: 7.1–49.3)% vs. 7.7 (IQR: 4.3–15.2)%, p = 0.008]. Multivariate Cox regression revealed that LA conduction time independently predicted AF recurrence following ablation over a median follow-up of 235 days [IQR: 154–382 days; hazard ratio (HR): 2.37, 95% confidence interval (CI): 1.08–5.23, p = 0.031]. The optimal cut-off for LA conduction time was 98 ms [area under curve (AUC): 0.926, sensitivity: 0.833, specificity: 0.894, p < 0.01]. Kaplan–Meier analysis revealed that patients with a conduction time >98 ms had a higher rate of AF recurrence following ablation (p < 0.001). Conclusions: Patients with longer LA conduction time after PVI had more frequent AF recurrence.

Abstract Background Cancer is currently the second leading cause of death globally. There is much uncertainty regarding the comparative risks of new‐onset overall cancer and pre‐specified cancer for Type 2 diabetes mellitus (T2DM) patients on sodium‐glucose cotransporter 2 inhibitors (SGLT2I) versus DPP4I. Methods This population‐based cohort study patients included patients who were diagnosed with T2DM and administered either SGLT2 or DPP4 inhibitors between 1 January 2015 and 31 December 2020 in public hospitals of Hong Kong. Results This study included 60,112 T2DM patients (mean baseline age: 62.1 ± 12.4 years, male: 56.36%), of which 18,167 patients were SGLT2I users and 41,945 patients were dipeptidyl peptidase 4 inhibitor (DPP4I) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of all‐cause mortality (HR: 0.92; 95% CI: 0.84–0.99; p= 0.04), cancer‐related mortality (HR: 0.58; 95% CI: 0.42–0.80; p ≤ 0.001) and new diagnoses of any cancer (HR: 0.70; 95% CI: 0.59–0.84; p ≤ 0.001). SGLT2I use was associated with a lower risk of new‐onset breast cancer (HR: 0.51; 95% CI: 0.32–0.80; p ≤ 0.001), but not of other malignancies. Subgroup analysis on the type of SGLT2I, dapagliflozin (HR: 0.78; 95% CI: 0.64–0.95; p = 0.01) and ertugliflozin (HR: 0.65; 95% CI: 0.43–0.98; p = 0.04) use was associated with lower risks of new cancer diagnosis. Dapagliflozin use was also linked to lower risks of breast cancer (HR: 0.48; 95% CI: 0.27–0.83; p = 0.001). Conclusion Sodium‐glucose cotransporter 2 inhibitor use was associated with lower risks of all‐cause mortality, cancer‐related mortality and new‐onset overall cancer compared to DPP4I use after propensity score matching and multivariable adjustment.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac ion channelopathy where the initial disease presentation is during childhood or adolescent stages, leading to increased risks of sudden cardiac death. Despite advances in medical science and technology, several gaps remain in the understanding of the molecular mechanisms, risk prediction, and therapeutic management of patients with CPVT. Recent studies have identified and validated seven sets of genes responsible for various CPVT phenotypes, including RyR2, CASQ-2, TRDN, CALM1, 2, and 3, and TECRL, providing novel insights into the molecular mechanisms. However, more data on atypical CPVT genotypes are required to investigate the underlying mechanisms further. The complexities of the underlying genetics contribute to challenges in risk stratification as well as the uncertainty surrounding nongenetic modifiers. Therapeutically, although medical management involving beta-blockers and flecainide, or insertion of an implantable cardioverter defibrillator remains the mainstay of treatment, animal and stem cell studies on gene therapy for CPVT have shown promising results. However, its clinical applicability remains unclear. Current gene therapy studies have primarily focused on the RyR2 and CASQ-2 variants, which constitute 75% of all CPVT cases. Alternative approaches that target a broader population, such as CaMKII inhibition, could be more feasible for clinical implementation. Together, this review provides an update on recent research on CPVT, highlighting the need for further investigation of the molecular mechanisms, risk stratification, and therapeutic management of this potentially lethal condition.

Abstract Background While immune checkpoint inhibitors (ICIs) are associated with elevated cardiovascular risks, evidence of any association between ICIs and myocardial infarction (MI) was scarce, especially in Asians. Methods Using prospectively collected population‐based data, this self‐controlled case series included patients prescribed an ICI between 1/1/2014 and 31/12/2020 in Hong Kong who had MI within January 1, 2013 to December 31, 2021. Incidence rate ratios (IRRs) for MI during and after ICI exposure were estimated, compared to the year before ICI initiation. Results Of 3684 identified ICI users, 24 had MI during the study period. MI incidence increased significantly in the first 90 days of exposure (IRR 3.59 [95% confidence interval: 1.31–9.83], p = 0.013), but not days 91–180 (p = 0.148) or ≥181 (p = 0.591) of exposure, nor postexposure (p = 0.923). Sensitivity analyses excluding patients with MI‐related death and incorporating extended exposure periods produced consistent results separately. Conclusions ICIs were associated with increased MI incidence in Asian Chinese patients during the first 90 days of use, but not later.

Abstract Background Androgen deprivation therapy (ADT), used increasingly in the treatment of prostate cancer (PCa), negatively influences glycemic control in diabetes and is associated with an increased risk of diabetes complications where hospitalization commonly ensues. Metformin could decrease the metabolic consequences of ADT and enhance its effect. This study examined the association of metformin use with healthcare resources utilization among diabetic, PCa patients receiving ADT. Methods Diabetic adults with PCa on ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with

Abstract Background Immune checkpoint inhibitors (ICIs) are increasingly established cancer therapeutics, but they are associated with new‐onset diabetes mellitus (DM). Such risks have not been adequately quantified, and between‐class and ‐sex differences remain unexplored. Methods This was a prospective cohort study of cancer patients receiving any ICI in Hong Kong between 2013 and 2021. Patients with known DM were excluded. Due to few patients using other ICIs, only programmed cell death 1 inhibitors (PD‐1i) and programmed death ligand 1 inhibitors (PD‐L1i) were compared, alongside between‐sex comparison. When comparing PD‐1i against PD‐L1i, patients with the use of other ICIs or both PD‐1i and PD‐L1 were further excluded. Inverse probability treatment weighting (IPTW) was used to minimize between‐group covariate imbalances. Results Altogether, 3375 patients were analyzed (65.2% males, median age 62.2 [interquartile range 53.8–69.5] years old). Over a median follow‐up of 1.0 [0.4–2.4] years, new‐onset DM occurred in 457 patients (13.5%), with a 3‐year risk of 14.5% [95% confidence interval 13.3%, 15.8%]. IPTW achieve acceptable covariate balance between sexes, and between PD‐1i (N = 622) and PD‐L1i (N = 2426) users. Males had significantly higher risk of new‐onset DM (hazard ratio 1.35 [1.09, 1.67], p = 0.006), while PD‐1i and PD‐L1i users did not have significantly different risks (hazard ratio vs PD‐L1i 0.81 [0.59, 1.11], p = 0.182). These were consistent in those with at least 1 year of follow‐up, and on competing risk regression. Conclusion Users of ICI may have a substantial risk of new‐onset DM, which may be higher in males but did not differ between PD‐1i and PD‐L1i.

Abstract Background P‐wave indices have been used to predict incident atrial fibrillation (AF), stroke, and mortality. However, such indices derived from automated ECG measurements have not been explored for their predictive values in heart failure (HF). We investigated whether automated P‐wave indices can predict adverse outcomes in HF. Methods This study included consecutive Chinese patients admitted to a single tertiary centre, presenting with HF but without prior AF, and with at least one baseline ECG, between 1 January 2010 and 31 December 2016, with last follow‐up of 31 December 2019. Results A total of 2718 patients were included [median age: 77.4, interquartile range (IQR): (66.9–84.3) years; 47.9 males]. After a median follow‐up of 4.8 years (IQR: 1.9–9.0 years), 1150 patients developed AF (8.8/year), 339 developed stroke (2.6/year), 563 developed cardiovascular mortality (4.3/year), and 1972 had all‐cause mortality (15.1/year). Compared with 101–120 ms as a reference, maximum P‐wave durations predicted new‐onset AF at ≤90 ms [HR: 1.17(1.11, 1.50), P

Abstract Aims Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline‐directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β‐blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. Methods This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple‐drug therapy (TT) and non‐triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Results Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all‐cause mortality (HR 0.656, 95% CI 0.447–0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380–0.946, P = 0.028), any‐cause rehospitalization (HR 0.687, 95% CI 0.541–0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565–0.948, P = 0.018). Conclusions In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF.

Introduction Feeding practices developed in early life can impact a child’s nutrition, growth, dental health, cognitive development and lifetime risk of chronic diseases. Substantial evidence suggests ethnic health inequalities, and non-recommended complementary infant feeding practices among UK’s South Asian (SA) population. Nurture Early for Optimal Nutrition aims to use women’s group participatory learning and action (PLA) cycles to optimise infant feeding, care and dental hygiene practices in SA infants

Background: Over the past few years, smartwatches have become increasingly popular in the monitoring of arrhythmias. Although the detection of atrial fibrillation with smartwatches has been the subject of various articles, there is no comprehensive research on the detection of arrhythmias other than atrial fibrillation. In this study, we included individual cases from the literature to identify the characteristics of patients with smartwatch-detected arrhythmias other than atrial fibrillation. Methods: PubMed, Embase, and SCOPUS were searched for case reports, case series, or cohort studies that reported individual participant-level data, until January 6, 2022. The following search string was used for each databases: ('Smart Watch' OR 'Apple Watch' OR 'Samsung Gear') AND ('Supraventricular Tachycardia' OR 'Cardiac Arrhythmia' OR 'Ventricular Tachycardia' OR 'Atrioventricular Nodal Reentry Tachycardia' OR 'Atrioventricular Reentrant Tachycardia' OR 'Heart Block' OR 'Atrial Flutter' OR 'Ectopic Atrial Tachycardia' OR 'Bradyarrhythmia'). Results: A total of 52 studies from PubMed, 20 studies from Embase, and 200 studies from SCOPUS were identified. After screening, 18 articles were included. A total of 22 patients were obtained from 14 case reports or case series. Four cohort studies evaluating various arrhythmias were included. Arrhythmias, including ventricular tachycardia, atrial fibrillation, atrial flutter, atrioventricular nodal reentry tachycardia, atrioventricular reentrant tachycardia, second- or third-degree atrioventricular block, and sinus bradycardia, were detected with smartwatches. Conclusions: Cardiac arrhythmias other than atrial fibrillation are also commonly detected with smartwatches. Smartwatches have an important potential besides traditional methods in the detection of arrhythmias and clinical practice.

Based on glucose levels, people fall into three groups, normal individuals, prediabetic patients, and diabetic mellitus (DM) patients. Prediabetes (pre-DM) is an intermediate condition that exists between normal glucose levels and DM. Atrial fibrillation (AF), one of the most prevalent cardiac arrhythmias in medical practice, contributes to a considerable morbidity and mortality rate. In this review, we looked at the clinical symptoms, pathological alterations, molecular mechanisms, and associated risk factors of pre-DM, type 2 DM (T2DM), and AF. In clinical practice, pre-DM can increase the prevalence of AF. In the hyperglycemic state, oxidative stress, inflammation, and endoplasmic reticulum stress can cause alterations in atrial cell or cardiac fibroblast function through tumor necrosis factor-α/nuclear factor-κB (NF-κB)/transforming growth factor-β, mitogen-activated protein kinase-matrix metalloproteinase-9 and PARP-1 is poly (ADP-ribose) polymerase 1. IκB kinase-α/NF-κB pathways, and further cause atria undergo structural, electrical, and neural remodeling which lead to the occurrence and persistence of AF. In addition, pre-DM and T2DM may worsen as a result of obesity, obstructive sleep apnea, and arterial hypertension. Furthermore, clinical researches have demonstrated that lifestyle interventions and/or pharmacotherapy in pre-DM patients can effectively delay the progresssion of pre-DM to T2DM. Individualized glycemic management and AF management should be provided to AF patients with pre-DM or DM.

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent ventricular trabeculations and deep intertrabecular recesses. Patients with LVNC have an increased risk of embolic events. The presence of symptoms at the time of diagnosis can be a risk marker for stroke/embolic events. Left ventricular ejection fraction (LVEF), as measured by transthoracic echocardiography and left atrial diameter, has been found to be a significant predictor of systemic embolism in LVNC patients. Furthermore, CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus and stroke or transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65–74 years and sex category [female]) scores were significantly higher in patients with stroke or embolism. Although the difference was not statistically significant, pediatric patients with LVNC combined with other congenital heart defects had more thromboembolic events compared to patients with isolated LVNC. On the other hand, stroke/transient ischemic attacks did not differ significantly between patients with isolated apical LVNC and mid-basal noncompaction. Furthermore, no differences in the prevalence of stroke between the quantiles of the maximal ratio of noncompacted to compacted myocardium have been revealed. Additionally, current data show no association between N-terminal pro-B-type natriuretic peptide levels and stroke/embolic events. Current evidence suggests anticoagulation treatment in LVNC patients with prior embolic events, atrial fibrillation, presence of left ventricular (LV) thrombus, and/or LV dysfunction. In patients with LVNC without a clear indication for anticoagulation, anticoagulant therapy may be considered in patients with CHADS2 score ≥2. More data are needed to identify patients at higher risk of embolic events who will be benefited from anticoagulation treatment.

Abstract Background Impaired left ventricular function is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The aim of this study is to evaluate the short-term changes of echocardiographic parameters, New York Heart Association (NYHA) class and B-type natriuretic peptide (BNP) level and adverse events amongst patients with heart failure (HF) after transcatheter aortic valve replacement (TAVR) procedure. Methods This was a retrospective cohort study conducted at affiliated Yantai Yuhuangding Hospital of Qingdao University between September 2017 and September 2022. TAVR cases were stratified into three groups [heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with preserved ejection fraction (HFpEF)] by left ventricular ejection fraction (LVEF). Baseline characteristics, changes in echocardiographic parameters (1 week and 1 month), BNP (1 month), and NYHA class (6 months) post-TAVR were compared across the three groups. Meanwhile, we observed the adverse events of the patients after TAVR. Results A total of 96 patients were included, of whom 15 (15.6%) had HFrEF, 15 (15.6%) had HFmrEF, and 66 (68.8%) had HFpEF. Compared to the HFpEF subgroup, patients in the HFrEF subgroup were younger (p

Abstract Background Previous studies have quantified repolarization variability using time-domain, frequency-domain and nonlinear analysis in mouse hearts. Here, we investigated the relationship between these parameters and ventricular arrhythmogenicity in a hypokalaemia model of acquired long QT syndrome. Methods Left ventricular monophasic action potentials (MAPs) were recorded during right ventricular regular 8 Hz pacing during normokalaemia (5.2 mM [K+]), hypokalaemia modeling LQTS (3 mM [K+]) or hypokalaemia with 0.1 mM heptanol in Langendorff-perfused mouse hearts. Results During normokalaemia, mean APD was 33.5 ± 3.7 ms. Standard deviation (SD) of APDs was 0.63 ± 0.33 ms, coefficient of variation was 1.9 ± 1.0% and the root mean square (RMS) of successive differences in APDs was 0.3 ± 0.1 ms. Low- and high-frequency peaks were 0.6 ± 0.5 and 2.3 ± 0.7 Hz, respectively, with percentage powers of 38 ± 22 and 61 ± 23%. Poincaré plots of APD n+1 against APD n revealed ellipsoid morphologies with SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6 ± 1.1. Approximate and sample entropy were 0.49 ± 0.12 and 0.64 ± 0.29, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.62 ± 0.27 and 0.60 ± 0.18, respectively. Hypokalaemia provoked ventricular tachycardia in six of seven hearts, prolonged APDs (51.2 ± 7.9 ms), decreased SD2/SD1 ratio (3.1 ± 1.0), increased approximate and sample entropy (0.68 ± 0.08 and 1.02 ± 0.33) and decreased short-term fluctuation slope (1.23 ± 0.20) (ANOVA, P

Abstract Introduction Cancer patients may be susceptible to poorer outcomes in COVID‐19 infection owing to the immunosuppressant effect of chemotherapy/radiotherapy and cancer growth, along with the potential for nosocomial transmission due to frequent hospital admissions. Methods This was a population‐based retrospective cohort study of COVID‐19 patients who presented to Hong Kong public hospitals between 1 January 2020 and 8 December 2020. The primary outcome was a composite endpoint of requirement for intubation, ICU admission and 30‐day mortality. Results The following study consisted of 6089 COVID‐19 patients (median age 45.9 [27.8.1–62.7] years; 50% male), of which 142 were cancer subjects. COVID‐19 cancer patients were older at baseline and tended to present with a higher frequency of comorbidities, including diabetes mellitus, hypertension, chronic obstructive pulmonary disease, ischemic heart disease, ventricular tachycardia/fibrillation and gastrointestinal bleeding (p

This population-based cohort study investigated the risk factors of incident dementia and vascular dementia in type 2 diabetic patients (≥45 years old) attending the Hong Kong Hospital Authority between 1st January and 31st December 2009.Of the 273,876 patients included,9994 showed incident dementia (median follow-up: 4245 days). Multivariable Cox regression identified older age (HR: 1.09 [95% CI: 1.08–1.10]) and antiplatelet use (HR: 1.36 [1.14–1.62]) as risk factors for incident dementia, and older age (HR: 1.07 [1.06–1.08]), ischemic stroke (HR: 1.47 [1.09–1.98]), fasting blood glucose (HR: 1.10 [1.01–1.20]), antiplatelets (HR: 1.92 [1.51–2.44]), and calcium channel blocker (HR: 1.28 [1.04–1.57]) use as risk factors of incident vascular dementia.

Summary: Peripheral arterial disease (PAD) is one of the leading causes of cardiovascular morbidity and mortality worldwide, yet current trials on therapeutic angiogenesis remain suboptimal. Type 2 immunity is critical for post-ischemic regeneration, but its regulatory role in revascularization is poorly characterized. Here, we show that type 2 cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), are the key mediators in post-ischemic angiogenesis. IL-4/IL-13-deficient mice exhibit impaired reperfusion and muscle repair in an experimental model of PAD. We find that deletion of IL-4Rα in the endothelial compartment, rather than the myeloid compartment, leads to remarkable impairment in revascularization. Mechanistically, IL-4/IL-13 promote endothelial cell proliferation, migration, and tube formation via IL-4Rα/STAT6 signaling. Furthermore, attenuated IL-4/IL-13 expression is associated with the angiogenesis deficit in the setting of diabetic PAD, while IL-4/IL-13 treatment rescues this defective regeneration. Our findings reveal the therapeutic potential of type 2 cytokines in treating patients with muscle ischemia.

Abstract Atrial cardiomyopathy refers to structural and electrical remodelling of the atria, which can lead to impaired mechanical function. While historical studies have implicated atrial fibrillation as the leading cause of cardioembolic stroke, atrial cardiomyopathy may be an important, underestimated contributor. To date, the relationship between atrial cardiomyopathy, atrial fibrillation, and cardioembolic stroke remains obscure. This review summarizes the pathogenesis of atrial cardiomyopathy, with a special focus on neurohormonal and inflammatory mechanisms, as well as the role of adipose tissue, especially epicardial fat in atrial remodelling. It reviews the current evidence implicating atrial cardiomyopathy as a cause of embolic stroke, with atrial fibrillation as a lagging marker of an increased thrombogenic atrial substrate. Finally, it discusses the potential of antithrombotic therapy in embolic stroke with undetermined source and appraises the available diagnostic techniques for atrial cardiomyopathy, including imaging techniques such as echocardiography, computed tomography, and magnetic resonance imaging as well as electroanatomic mapping, electrocardiogram, biomarkers, and genetic testing. More prospective studies are needed to define the relationship between atrial cardiomyopathy, atrial fibrillation, and embolic stroke and to establish a prompt diagnosis and specific treatment strategies in these patients with atrial cardiomyopathy for the secondary and even primary prevention of embolic stroke.

Abstract Background The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship. Methods Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006–2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000–2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations. Results In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09–1.39), P Trend

Abstract Cardiovascular diseases are one of the leading global causes of mortality. Currently, clinicians rely on their own analyses or automated analyses of the electrocardiogram (ECG) to obtain a diagnosis. However, both approaches can only include a finite number of predictors and are unable to execute complex analyses. Artificial intelligence (AI) has enabled the introduction of machine and deep learning algorithms to compensate for the existing limitations of current ECG analysis methods, with promising results. However, it should be prudent to recognize that these algorithms also associated with their own unique set of challenges and limitations, such as professional liability, systematic bias, surveillance, cybersecurity, as well as technical and logistical challenges. This review aims to increase familiarity with and awareness of AI algorithms used in ECG diagnosis, and to ultimately inform the interested stakeholders on their potential utility in addressing present clinical challenges.

Abstract Background Early repolarization syndrome (ERS) and Brugada syndrome (BrS) are both J-wave syndromes. Both can involve mutations in the SCN5A gene but may exhibit distinct electrocardiographic (ECG) differences. The aim of this systematic review and meta-analysis is to investigate possible differences in ECG markers between SCN5A-positive patients with ERS and BrS. Methods PubMed and Embase were searched from their inception to 20 October 2021 for human studies containing the search terms “SCN5A” and “variant” and “early repolarization” or “Brugada”, with no language restrictions. Continuous variables were expressed as mean±standard deviation. PR interval, QRS duration, QTc and heart rate from the included studies were pooled to calculate a mean for each variable amongst BrS and ERS patients. A two-tailed Student’s t test was then performed to for comparisons. Results A total of 328 studies were identified. After full-text screening, 12 studies met our inclusion criteria and were included in this present study. One hundred and four ERS patients (mean age 30.86±14.45) and 2000 BrS patients (mean age 36.17±11.39) were studied. Our meta-analysis found that ERS patients had shorter QRS duration (90.40±9.97 vs. 114.79±20.10, P = 0.0001) and shorter corrected QT intervals (QTc) with borderline significance (393.63±40.04 vs. 416.82±37.43, P = 0.052). By contrast, no significant differences in baseline heart rate (65.15±18.78 vs. 76.06±18.78, P = 0.068) or PR intervals (197.40±34.69 vs. 191.88±35.08, P = 0.621) were observed between ERS and BrS patients. Conclusion BrS patients with positive SCN5A mutations exhibited prolonged QRS, indicating conduction abnormalities, whereas ERS patients with positive SCN5A mutations showed normal QRS. By contrast, whilst QTc intervals were longer in BrS than in ERS SCN5A positive patients, they were within normal limits. Further studies are needed to examine the implications of these findings for arrhythmic risk stratification.

Background: Routinely collected health data are increasingly used in clinical research. No study has systematically reviewed the temporal trends in the number of publications and analyzed different aspects of local research practices and their variations in Hong Kong, China, with a specific focus on research ethics governance and approval. Methods: PubMed was systematically searched from its inception to March 28, 2023, for studies using routinely collected healthcare data from Hong Kong. Results: A total of 454 studies were included. Between 2000 and 2009, 32 studies were identified. The number of publications increased from 5 to 120 between 2010 and 2022. Of the investigator-led studies using the Hospital Authority (HA)’s cross-cluster data (n = 393), 327 (83.2%) reported receiving ethics approval from a single cluster/university-based REC, whereas 50 studies (12.7%) did not report approval from a REC. For use of the HA Data Collaboration Lab, approval by a single hospital-based or University-based REC is accepted. Repeated submission of identical ethics applications to different RECs is estimated to cost HK$4.2 million yearly. Conclusions: Most studies reported gaining approval from a single cluster REC before retrieval of cross-cluster HA data. Substantial cost savings would result if repeated review of identical ethics applications were not required.

A growing body of evidence on a wide spectrum of adverse cardiac events following oncologic therapies has led to the emergence of cardio-oncology as an increasingly relevant interdisciplinary specialty. This also calls for better risk-stratification for patients undergoing cancer treatment. Machine learning (ML), a popular branch discipline of artificial intelligence that tackles complex big data problems by identifying interaction patterns among variables, has seen increasing usage in cardio-oncology studies for risk stratification. The objective of this comprehensive review is to outline the application of ML approaches in cardio-oncology, including deep learning, artificial neural networks, random forest and summarize the cardiotoxicity identified by ML. The current literature shows that ML has been applied for the prediction, diagnosis and treatment of cardiotoxicity in cancer patients. In addition, role of ML in gender and racial disparities for cardiac outcomes and potential future directions of cardio-oncology are discussed. It is essential to establish dedicated multidisciplinary teams in the hospital and educate medical professionals to become familiar and proficient in ML in the future.

Abstract Aims This study aimed to compare the rates of major cardiovascular adverse events in sodium‐glucose cotransporter‐2 inhibitors (SGLT2I) and dipeptidyl peptidase‐4 inhibitors (DPP4I) users in a Chinese population. SGLT2I and DPP4I are increasingly prescribed for type 2 diabetes mellitus patients. However, few population‐based studies are comparing their effects on incident heart failure or myocardial infarction. Methods and results This was a population‐based retrospective cohort study using the electronic health record database in Hong Kong, including type 2 diabetes mellitus patients receiving either SGLT2I or DPP4I from 1 January 2015 to 31 December 2020. Propensity score matching was performed in a 1:1 ratio based on demographics, past comorbidities, and non‐SGLT2I/DPP4I medications with nearest neighbour matching (caliper = 0.1). Univariable and multivariable Cox models were used to identify significant predictors for new‐onset heart failure, new‐onset myocardial infarction, cardiovascular mortality, and all‐cause mortality. Sensitivity analyses with competing risk models and multiple propensity score matching approaches were conducted. A total of 41 994 patients (58.89% males, median admission age at 58 years old, interquartile range [IQR]: 51.2–65.3) were included with a median follow‐up of 5.6 years (IQR: 5.32–5.82). In the matched cohort, SGLT2I use was significantly associated with lower risks of new‐onset heart failure (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: [0.66, 0.81], P

Abstract Ventricular arrhythmias (VAs) and sudden cardiac death (SCD) are significant adverse events that affect the morbidity and mortality of both the general population and patients with predisposing cardiovascular risk factors. Currently, conventional disease-specific scores are used for risk stratification purposes. However, these risk scores have several limitations, including variations among validation cohorts, the inclusion of a limited number of predictors while omitting important variables, as well as hidden relationships between predictors. Machine learning (ML) techniques are based on algorithms that describe intervariable relationships. Recent studies have implemented ML techniques to construct models for the prediction of fatal VAs. However, the application of ML study findings is limited by the absence of established frameworks for its implementation, in addition to clinicians’ unfamiliarity with ML techniques. This review, therefore, aims to provide an accessible and easy-to-understand summary of the existing evidence about the use of ML techniques in the prediction of VAs. Our findings suggest that ML algorithms improve arrhythmic prediction performance in different clinical settings. However, it should be emphasized that prospective studies comparing ML algorithms to conventional risk models are needed while a regulatory framework is required prior to their implementation in clinical practice.

Abstract Background and Objectives Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk‐scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome. Findings Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted. Conclusions Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female‐specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender‐specific risk stratification approach amongst asymptomatic BrS patients.

Background Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior–inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. Conclusions In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure.

Abstract Introduction Neutrophil‐to‐lymphocyte ratio (NLR) is a routinely available biomarker that reflects systemic inflammation. The study evaluated the predictive value of NLR for ischemic stroke and atrial fibrillation (AF) in patients with type 2 diabetes mellitus. Methods This was a population‐based cohort study of patients with type 2 diabetes mellitus and complete blood count tests at baseline between 1 January 1st, 2009, and 31 December, 2009, at government‐funded hospitals/clinics in Hong Kong. Follow‐up was until 31 December, 2019, or death. Results A total of 85,351 patients (age = 67.6 ± 13.2 years old, male = 48.8%, follow‐up = 3101 ± 1441 days) were included. Univariable Cox regression found that increased NLR at quartiles 2, 3 and 4 was significantly associated with higher risks of new‐onset ischemic stroke (hazard ratio [HR]: 1.28 [1.20–1.37], p

Summary: Background: Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever. Methods: A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively. Findings: In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5–81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS. Interpretation: In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever. Funding: None.

Background: Dipeptidyl peptidase-4 inhibitors (DPP4I) may be associated with higher risks of acute pancreatitis and pancreatic cancer. This study compared the risks of acute pancreatitis and pancreatic cancer between sodium glucose cotransporter 2 inhibitors (SGLT2I) and DPP4I users. Methods: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus on either SGLT2I or DPP4I between January 1st, 2015, and December 31st 2020 in Hong Kong. The primary outcome was new-onset acute pancreatitis and pancreatic cancer. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regressions were applied to identify significant predictors. Results: This cohort included 31609 Type 2 Diabetes Mellitus patients (median age: 67.4 years old [SD: 12.5]; 53.36% males). 6479 patients (20.49%) used SGLT2I, and 25130 patients (70.50%) used DPP4I. After matching, the rate of acute pancreatitis was significantly lower in SGLT2I users compared to DPP4I users. Multivariable Cox regression showed that SGLT2I use was associated with lower risks of acute pancreatitis (Hazard ratio, HR: 0.11; 95% Confidence interval, CI: 0.02-0.51; P=0.0017) and pancreatic cancer (HR: 0.22; 95% CI: 0.039-0.378; P=0.0003). The results were consistent using competing risk models and different propensity score approaches. Conclusions: SGLT2I use was associated with lower risks of new-onset acute pancreatitis and pancreatic cancer after propensity score matching and multivariable adjustment, underscoring the need for further evaluation in the randomised controlled trial setting.

Abstract Background Programmed death-1 (PD-1) and programmed death- ligand 1 (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors. Methods Patients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at publicly funded hospitals of Hong Kong, China, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction, atrial fibrillation, or atrial flutter with the last follow-up date of 31st December 2020. Propensity score matching between PD-L1 inhibitor use and PD-1 inhibitor use with a 1:2 ratio for patient demographics, past comorbidities and non-PD-1/PD-L1 medications was performed with nearest neighbour search strategy (0.1 caliper). Univariable and multivariable Cox regression analysis models were conducted. Competing risks models and multiple propensity matching approaches were considered for sensitivity analysis. Results A total of 1959 patients were included. Over a median follow-up of 247 days (interquartile range [IQR]: 72-506), 320 (incidence rate [IR]: 16.31%) patients met the primary outcome after PD-1/PD-L1 treatment: 244 (IR: 12.57%) with heart failure, 38 (IR: 1.93%) with acute myocardial infarction, 54 (IR: 2.75%) with atrial fibrillation, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with lower risks of the composite outcome both before (hazard ratio [HR]: 0.32, 95% CI: [0.18-0.59], P value=0.0002) and after matching (HR: 0.34, 95% CI: [0.18-0.65], P value=0.001), and lower all-cause mortality risks before matching (HR: 0.77, 95% CI: [0.64-0.93], P value=0.0078) and after matching (HR: 0.80, 95% CI: [0.65-1.00], P value=0.0463). Patients who developed cardiac complications had shorter average readmission intervals and a higher number of hospitalizations after treatment with PD-1/PD-L1 inhibitors in both the unmatched and matched cohorts (P value

Abstract Aims The angiotensin receptor–neprilysin inhibitor (ARNI), sacubitril/valsartan, confers additional protective effects compared with angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) in terms of reversed left ventricular (LV) remodelling and improves the prognosis of patients with heart failure (HF). However, few studies have examined the effects of ARNI on the left atrium. Accordingly, this study compared the effects of ARNI and ACEI/ARB on left atrial (LA) remodelling in heart failure with reduced ejection fraction (HFrEF). Methods and results This was a single‐centre retrospective study of patients with HFrEF hospitalized at the First Affiliated Hospital of Dalian Medical University between 26 February 2016 and 8 July 2020. Patients were classified into ARNI and ACEI/ARB groups and further subgroups based on the left atrial volume index (LAVI): mildly abnormal (29 mL/m2 ≤ LAVI

Background: Transcatheter aortic valve replacement (TAVR) is an effective alternative treatment for patients with aortic stenosis (AS) who have intermediate to high surgical risk or who are inoperable. However, the incidence of conduction abnormalities is high after TAVR, which can reduce the effectiveness of the surgery. Our research objective is to explore the risk factors of new-onset conduction abnormalities after TAVR, providing reference value for clinical doctors to better prevent and treat conduction abnormalities. Methods: Patients who underwent TAVR were divided into those who developed heart block and those who did not. Baseline clinical characteristics, cardiac structural parameters, procedural characteristics, electrocardiogram (ECG) changes before and after TAVR (△ = postoperative minus preoperative), and surgical complications were compared. Logistic regression was applied to identify significant risk factors for new-onset heart block. Results: We studied 93 patients, of whom 34.4% developed heart blocks. Univariate logistic regression showed that prior history of malignancy, atrial fibrillation, preoperative high-level total cholesterol and low-density lipoprotein cholesterol (LDL-C), △HR, △QRS interval, △QT interval, and △QTc interval were risk factors of new-onset heart block after TAVR. Multivariate analysis showed that preoperative high-level LDL-C and △QRS interval remained significant independent risk factors after adjusting for potential confounds. Conclusions: Heart block is the most common complication of TAVR, and its significant independent risk factors include high-level LDL-C and △QRS interval.

Despite considerable breakthroughs in Parkinson’s disease (PD) research, understanding of non-motor symptoms (NMS) in PD remains limited. The lack of basic level models that can properly recapitulate PD NMS either in vivo or in vitro complicates matters. Even so, recent research advances have identified cardiovascular NMS as being underestimated in PD. Considering that a cardiovascular phenotype reflects sympathetic autonomic dysregulation, cardiovascular symptoms of PD can play a pivotal role in understanding the pathogenesis of PD. In this study, we have reviewed clinical and non-clinical published papers with four key parameters: cardiovascular disease risks, electrocardiograms (ECG), neurocardiac lesions in PD, and fundamental electrophysiological studies that can be linked to the heart. We have highlighted the points and limitations that the reviewed articles have in common. ECG and pathological reports suggested that PD patients may undergo alterations in neurocardiac regulation. The pathological evidence also suggested that the hearts of PD patients were involved in alpha-synucleinopathy. Finally, there is to date little research available that addresses the electrophysiology of in vitro Parkinson’s disease models. For future reference, research that can integrate cardiac electrophysiology and pathological alterations is required.

Background: Lung cancer is one of the major cause of death globally. Crizotinib is a first-line drug used in treating non-small-cell lung cancer (NSCLC). However, the pathophysiological mechanisms underlying its cardiotoxicity are unknown. This study investigated the mechanisms of crizotinib-induced cardiotoxicity and explored whether this toxicity can be prevented by the angiotensin receptor/neprilysin inhibitor sacubitril/valsartan. Methods: Male C57BL/6 mice were randomly divided into three groups: control, crizotinib (40 mg⋅kg-1⋅d-1 for four weeks), and crizotinib + sacubitril/valsartan (40 mg⋅kg-1⋅d-1/60 mg⋅kg-1⋅d-1 for four weeks). Expression of genes in myocardial tissue were detected by transcriptomic sequencing, with verification of the differentially expressed genes (DEGs) using Real time-polymerase chain reaction (RT-PCR). Blood pressure (BP) and cardiac function of animals were measured using non-invasive monitoring and echocardiography approaches. Ventricular refractory period (RP), as well as the induction rate and score of ventricular arrhythmias (VAs) were detected by in vivo electrophysiology. Epicardial conductance was measured by mapping. Expression of Myh7 in myocardium was detected by western blot and RT-PCR. Results: DEGs detected using transcriptomic sequencing included 10 up-regulated and 20 down-regulated genes. The first 5 DEGs identified were Myh7, Ngp, Lcn2, Ciart and Ptgds. Kyoto Encyclopedia of Genes and Genomes (KEGG) result indicated that Myh7 is involved in myocarditis, cardiomyopathy, and cardiac muscle contraction. Crizotinib treatment increased blood pressure, prolonged QTc interval, shortened ventricular RP, increased the incidence and score of right VAs, and increased Myh7 expression. Most of these responses were limited by sacubitril/valsartan. Conclusions: Crizotinib induced a range of cardiotoxic side effects in a mouse model and increased Myh7 expression represents a biomarker for this response. These cardiovascular toxic responses can be largely prevented by sacubitril/valsartan.

Abstract Aims There is an emerging interest in elucidating the natural history and prognosis for patients with heart failure with reduced ejection fraction (HFrEF) in whom left ventricular ejection fraction (LVEF) subsequently improves. The characteristics and outcomes were compared between heart failure with recovered ejection fraction (HFrecEF) and persistent HFrEF. Methods and results This is a retrospective study of adults who underwent at least two echocardiograms 3 months apart between 1 November 2015 and 31 October 2019 with an initial diagnosis of HFrEF. The subjects were divided into HFrecEF group (second LVEF > 40%, ≥10% absolute improvement in LVEF) and persistent HFrEF group (20% subgroups. The primary outcomes were all‐cause mortality and rehospitalization. A total of 1160 HFrEF patients were included [70.2% male, mean (standard deviation) age: 62 ± 13 years]. On the second echocardiogram, 284 patients (24.5%) showed HFrecEF and 876 patients (75.5%) showed persistent HFrEF. All‐cause mortality was identified in 23 (8.10%) HFrecEF and 165 (18.84%) persistent HFrEF, whilst 76 (26.76%) and 426 (48.63%) showed rehospitalizations, respectively. Survival analysis showed that the persistent HFrEF subgroup experienced a significantly higher mortality at 12 and 24 months and a higher hospitalization at 12, 24, 48, and more than 48 months following discharge. Multivariate Cox regression showed that persistent HFrEF had a higher risk of all‐cause mortality [hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.49–3.56, P = 0.000] and rehospitalization (HR 1.85, 95% CI 1.45–2.36, P = 0.000) than the HFrecEF group. Subgroup analysis showed that the LVEF ≥ 20% improvement subgroup had lower rates of adverse outcomes compared with those with less improvement of 10–20%. Conclusions Heart failure with recovered ejection fraction is a distinct HF phenotype with better clinical outcomes compared with those with persistent HFrEF. HFrecEF patients have a relatively better short‐term mortality at 24 months but not thereafter.