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Aim: To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM).Methods: Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality.Results: Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality.Conclusion: Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

To investigate for potential protective effects of statin use among patients with infective endocarditis (IE) with consideration for underlying diseases and bacterial culture - variables which have prognostic implications and show considerable geographic variation yet are unappreciated in previous pharmacoepidemiological studies.Patients diagnosed with IE between January 1, 1996, and December 31, 2019, were identified. We estimated the effect on mortality of pre-admission statin use (≥90 cumulative days of use before index date) and in-hospital use (use beginning within 2 days of admission), compared with nonusers and discontinued users, respectively, through propensity score analytics.Of 6700 IE patients (mean age, 58.0 years; 63.3% male [n=4251]), 776 patients had pre-admission statin use, with 626 continuing statin use following admission (in-hospital users). Pre-admission statin users had a 31% lower risk of 1-year mortality (HR, 0.69; 95% CI, 0.58 to 0.82) compared with nonusers. In-hospital users had a 48% lower risk of 1-year mortality (HR, 0.52; 95% CI, 0.34 to 0.78) compared with discontinued users. Subgroup analyses showed significant protective effects of statin use for patients with varying causative agents, underlying diseases, and with or without prosthetic valves. Results were consistent across different statins, and were dose-dependent.In patients with IE, pre-admission and in-hospital use of statin, when compared with statin nonusers and discontinued users, respectively, were associated with a lower risk of 1-year mortality.

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).Conclusion: Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Our recent work shows that periodontitis experience reflects host susceptibility to the onset of multiple systemic diseases and conditions. This cross-sectional study further investigated whether and to what extent the existing periodontitis could reflect the concurrent presence of inflammatory comorbidities among 'self-perceived health' individuals.There were 115 'self-perceived health' adults who completed a questionnaire on demographic characteristics and lifestyles. Twenty medical diagnostic tests were then performed to detect eight common systemic diseases and conditions. Meanwhile, full-mouth periodontal examination was undertaken, and the subjects were classified as two subgroups with or without Generalized Severe Periodontitis (Stages III/IV, generalized). The interlink of periodontal status and concurrent systemic comorbidities was assessed.98.3% (113/115) of the subjects exhibited at least one undiagnosed systemic disease/disorder. Of them, 52.2% (59/113) and 47.8% (54/113) concurrently presented with 1-5 or ≥6 abnormal test results, respectively. Overall, 96.5% (111/115) had periodontitis. Generalized Severe Periodontitis was present in 43.2% (48/111) of the periodontitis patients, and it was significantly associated with the profiles of abnormal test results after adjusting potential confounders (abnormal test results 1-5 vs ≥6; OR: 3.23, p = .012).The present study shows that existing severe periodontitis could well reflect the concurrent presence of multiple inflammatory comorbidities. Oral and medical professionals can play proactive roles in enhancing health awareness and healthcare, through strong collaboration and teamwork.

Aims: Patients with atrial fibrillation (AF) have a higher risk of ischemic stroke or systemic embolism with a greater risk for female patients. This study aims to evaluate the risk of ischemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences.Methods and results: Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischemic stroke or systemic embolism or bleeding in the inpatient setting between February 23, 2021 and March 31, 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with ten controls according to sex, age, Charlson comorbidity index and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis and conditional logistic regression was used in nested case-control analysis to assess the risks and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days (incidence rate ratio 6.60[95% CI 1.51-28.77]) and 14-27 days (6.53[95% CI 1.31-32.51]), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21 [95% CI 1.14-33.91]) and 14-27 days (5.52 [95% CI 1.12-27.26]) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88 [95% CI 1.67-9.03]) in the nested case-control analysis. No increased risk of ischemic stroke or systemic embolism was identified in male patients and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42 [95% CI 5.08-59.73]) and males (6.63 [95% CI 2.02-21.79]).Conclusions: The risk of ischemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection. AIMS: Patients with atrial fibrillation (AF) have a higher risk of ischemic stroke or systemic embolism with a greater risk for female patients. This study aims to evaluate the risk of ischemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences.METHODS AND RESULTS: Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischemic stroke or systemic embolism or bleeding in the inpatient setting between February 23, 2021 and March 31, 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with ten controls according to sex, age, Charlson comorbidity index and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis and conditional logistic regression was used in nested case-control analysis to assess the risks and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days (incidence rate ratio 6.60[95% CI 1.51-28.77]) and 14-27 days (6.53[95% CI 1.31-32.51]), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21 [95% CI 1.14-33.91]) and 14-27 days (5.52 [95% CI 1.12-27.26]) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88 [95% CI 1.67-9.03]) in the nested case-control analysis. No increased risk of ischemic stroke or systemic embolism was identified in male patients and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42 [95% CI 5.08-59.73]) and males (6.63 [95% CI 2.02-21.79]).CONCLUSIONS: The risk of ischemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection.

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

Aims This study aims to evaluate the short- and long-term associations between COVID-19 and development of cardiovascular disease (CVD) outcomes and mortality in the general population. Methods and Results A prospective cohort of patients with COVID-19 infection between 16 March 2020 and 30 November 2020 was identified from UK Biobank, and followed for up to 18 months, until 31 August 2021. Based on age (within 5 years) and sex, each case was randomly matched with up to 10 participants without COVID-19 infection from two cohorts—a contemporary cohort between 16 March 2020 and 30 November 2020 and a historical cohort between 16 March 2018 and 30 November 2018. The characteristics between groups were further adjusted with propensity score-based marginal mean weighting through stratification. To determine the association of COVID-19 with CVD and mortality within 21 days of diagnosis (acute phase) and after this period (post-acute phase), Cox regression was employed. In the acute phase, patients with COVID-19 (n = 7584) were associated with a significantly higher short-term risk of CVD {hazard ratio (HR): 4.3 [95% confidence interval (CI): 2.6– 6.9]; HR: 5.0 (95% CI: 3.0–8.1)} and all-cause mortality [HR: 81.1 (95% CI: 58.5–112.4); HR: 67.5 (95% CI: 49.9–91.1)] than the contemporary (n = 75 790) and historical controls (n = 75 774), respectively. Regarding the post-acute phase, patients with COVID-19 (n = 7139) persisted with a significantly higher risk of CVD in the long-term [HR: 1.4 (95% CI: 1.2–1.8); HR: 1.3 (95% CI: 1.1– 1.6)] and all-cause mortality [HR: 5.0 (95% CI: 4.3–5.8); HR: 4.5 (95% CI: 3.9–5.2) compared to the contemporary (n = 71 296) and historical controls (n = 71 314), respectively. Conclusions COVID-19 infection, including long-COVID, is associated with increased short- and long-term risks of CVD and mortality. Ongoing monitoring of signs and symptoms of developing these cardiovascular complications post diagnosis and up till at least a year post recovery may benefit infected patients, especially those with severe disease.

OBJECTIVE To evaluate the association between prediabetes and heart failure (HF) and the association of HF with changes in glycemic status. RESEARCH DESIGN AND METHODS Patients newly diagnosed with atrial fibrillation (AF) between 2015 and 2018 were divided into three groups (normoglycemia, prediabetes, and type 2 diabetes) according to their baseline glycemic status. The primary outcome was incident HF. The Fine and Gray competing risks model was applied, with death defined as the competing event. RESULTS Among 17,943 patients with AF (mean age 75.5 years, 47% female), 3,711 (20.7%) had prediabetes, and 10,127 (56.4%) had diabetes at baseline. Over a median follow-up of 4.7 years, HF developed in 518 (14%) patients with normoglycemia, 646 (15.7%) with prediabetes, and 1,795 (17.7%) with diabetes. Prediabetes was associated with an increased risk of HF compared with normoglycemia (subdistribution hazard ratio [SHR] 1.12, 95% CI 1.03–1.22). In patients with prediabetes at baseline, 403 (11.1%) progressed to diabetes, and 311 (8.6%) reversed to normoglycemia at 2 years. Compared with remaining prediabetic, progression to diabetes was associated with an increased risk of HF (SHR 1.50, 95% CI 1.13–1.97), whereas reversion to normoglycemia was associated with a decreased risk (SHR 0.61, 95% CI 0.42–0.94). CONCLUSIONS Prediabetes was associated with an increased risk of HF in patients with AF. Compared with patients who remained prediabetic, those who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who reversed to normoglycemia incurred a lower risk of HF.

Aims: We investigated titration patterns of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) and beta-blockers, quality of life (QoL) over 6 months, and associated 1 year outcome [all-cause mortality/heart failure (HF) hospitalization] in a real-world population with HF with reduced ejection fraction (HFrEF). Methods and results: Participants with HFrEF (left ventricular ejection fraction 80% of patients, mineralocorticoid receptor antagonist in about half of patients, and statins in >90% of patients. At baseline, only 11% and 9% received 100% GRD for each drug class, respectively, with about half (47%) achieving ≥50% GRD for ACEis/ARBs or beta-blockers. At 6 months, a large majority remained in the ‘stay low’ category, one third remained in ‘stay high’, whereas 10–16% up-titrated and 4–6% down-titrated. Patients with lower (vs. higher) N-terminal pro-beta-type natriuretic peptide levels were more likely to be up-titrated or be in ‘stay high’ for ACEis/ARBs and beta-blockers (P = 0.002). Ischaemic aetiology, prior HF hospitalization, and enrolment in Singapore (vs. New Zealand) were independently associated with higher odds of ‘staying low’ (all P

Context Individuals with type 2 diabetes mellitus (DM) have an increased risk of pneumonia and septic shock. Traditional glucose-lowering drugs have recently been found to be associated with a higher risk of infections. It remains unclear whether sodium-glucose cotransporter 2 inhibitors (SGLT2is), which have pleiotropic/anti-inflammatory effects, may reduce the risk of pneumonia and septic shock in DM. Methods MEDLINE, Embase, and ClinicalTrials.gov were searched from inception up to May 19, 2022, for randomized, placebo-controlled trials of SGLT2i that included patients with DM and reported outcomes of interest (pneumonia and/or septic shock). Study selection, data extraction, and quality assessment (using the Cochrane Risk of Bias Assessment Tool) were conducted by independent authors. A fixed-effects model was used to pool the relative risk (RRs) and 95% CI across trials. Results Out of 4568 citations, 26 trials with a total of 59 264 patients (1.9% developed pneumonia and 0.2% developed septic shock) were included. Compared with placebo, SGLT2is significantly reduced the risk of pneumonia (pooled RR 0.87, 95% CI 0.78-0.98) and septic shock (pooled RR 0.65, 95% CI 0.44-0.95). There was no significant heterogeneity of effect size among trials. Subgroup analyses according to the type of SGLT2i used, baseline comorbidities, glycemic control, duration of DM, and trial follow-up showed consistent results without evidence of significant treatment-by-subgroup heterogeneity (all Pheterogeneity > .10). Conclusion Among DM patients, SGLT2is reduced the risk of pneumonia and septic shock compared with placebo. Our findings should be viewed as hypothesis generating, with concepts requiring validation in future studies.

Aim: The organ protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors may be beneficial against infectious complications. This real-world study aims to compare the risk of pneumonia and sepsis between SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with type 2 diabetes.Methods: Using a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System [CDARS]), we included patients initiated on SGLT2 inhibitors or DPP-4 inhibitors between January 01, 2015 and December 31, 2019 through 1:2 propensity score matching. The primary outcomes were incident events of pneumonia, sepsis and the related mortality. Cox proportional hazards analysis was used to compare the risk of incident pneumonia and sepsis for SGLT2 inhibitors versus DPP-4 inhibitors.Results: After propensity score matching, 10,706 new users of SGLT2 inhibitors and 18,281 new users of DPP-4 inhibitors were included. The mean age of all eligible subjects were 60 years (SD 11.07) and 61.1% were male. There were 309 pneumonia events [incidence rate per 1000 person-years (IR) = 11.38] among SGLT2 inhibitors users and 961 events (IR = 20.45) among DPP-4 inhibitors users, with lower risk of pneumonia among SGLT2 inhibitors users (adjusted HR 0.63 [95%CI 0.55–0.72], pConclusion: We provide real-world evidence that irrespective of age, sex, prior-existing cardiovascular disease, or type of SGLT2 inhibitors used, patients with type 2 diabetes initiated on SGLT2 inhibitors have lower incidence of pneumonia and sepsis as well as mortality risk associated with pneumonia, sepsis, and infectious diseases, compared with those initiated on DPP-4 inhibitors.

Increased serum uric acid (SUA) is common in type 2 diabetes mellitus (T2DM) and is associated with left ventricular (LV) myocardial dysfunction. Nonetheless the association of SUA with right ventricular (RV) function in T2DM has not been studied. This study aimed to investigate the association of SUA with biventricular myocardial function in patients with T2DM.A total of 560 patients with T2DM were enrolled and divided into four groups according to sex-specific quartiles of SUA. Transthoracic echocardiography was performed and two-dimensional speckle tracking was used to measure biventricular myocardial strain, including LV global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and RV free wall longitudinal strain (RV-FWLS). The absolute value of all biventricular strain parameters showed a stepwise decrease across SUA quartiles (all P 0.01). In particular, LV assessment by GLS, CS and RS demonstrated that those in the 4th quartile were impaired compared with the other quartiles (all P 0.05). Similarly, RV-FWLS of the 4th quartile was significantly impaired compared with the 1st and 2nd quartiles (all P 0.05). The same reduction in biventricular strain across SUA quartiles was observed in patients with estimated glomerular filtration rate or ≥60 ml/min/1.73 mSUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control.

Iokfai Cheang,1,2,&ast; Xu Zhu,1,&ast; Xinyi Lu,1 Xin Yue,1 Yuan Tang,1 Rongrong Gao,1 Shengen Liao,1 Wenming Yao,1 Yanli Zhou,1 Haifeng Zhang,1,3 Kai-Hang Yiu,2,4 Xinli Li1 1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China; 2Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, 999077, People’s Republic of China; 3Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, People’s Republic of China; 4Division of Cardiology, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Li, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China, Tel +86 13611573111, Email xinli3267@njmu.edu.cn Kai-Hang Yiu, Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, 999077, People’s Republic of China, Tel +852 22553633, Fax +852 28186304, Email khkyiu@hku.hkBackground: Inflammation is one of the major pathways in the progression of hypertension (HTN), and the related inflammatory markers have demonstrated certain predictive values. The current study aimed to integrate these markers to construct an inflammatory prognostic scoring (IPS) system and to assess the prognostic values of IPS in patients with HTN.Methods: A total of 9846 adult participants with HTN from NHANES 1999– 2010 were enrolled and followed up. Demographic characteristics and the related laboratory results for the 12 inflammatory markers were collected. LASSO-COX regression, Kaplan–Meier, restricted cubic spline COX regression (RCS), receiver operator characteristic curve (ROC), and random survival forests (RSF) analysis were applied to explore the values of individual and IPS parameters.Results: At the census date of follow-up, 2387 (24.2%) were identified as all-cause deaths and 484 (4.9%) as cardiovascular deaths. All inflammatory markers showed certain prognostic values. Then, based on the LAASO analysis, LDH, ALP, LYM, NLR, MLR, SIRI, and RDW were included in the construction of the IPS system. The higher IPS had significantly worse long-term prognosis in Kaplan–Meier analysis (p log-rank < 0.001). Also, IPS remained an independent prognosticator compared to the lowest quartile (All p for trend < 0.001), and the ROC showed satisfactory values in the long-term prognosis of both cardiovascular and all-cause mortality. RCS further showed a linear association of IPS with cardiovascular mortality and all-cause mortality (p for non-linearity > 0.05). Two different algorithms of RSF, variable importance and minimal depth, to evaluate the prognostic importance showed that IPS was the best in survival prediction.Conclusion: Our results highlight that a higher IPS (system integrating the inflammatory markers) was associated with the increased risk of cardiovascular and all-cause mortality in patients with HTN, suggesting that IPS is a useful method for risk stratification in HTN.Keywords: hypertension, HTN, inflammation, inflammatory prognostic scoring system, prognosis, random survival forest

This study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD).Patients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI 1.4. The prognosis of CMD as determined by MPRI is unknown.Chest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke.A total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p 0.001).Stress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.

Singular value decomposition (SVD)-based filters have become the norm for clutter filtering in ultrasound blood flow applications but are computationally expensive and susceptible to large and fast tissue motion. Randomized SVD (rSVD) has later been shown to successfully accelerate filtering of in vivo stationary tissues. However, little is known about its performance on ultrafast echocardiography, which produces thousands of frames to assess complex myocardial deformation and blood dynamics. Neither has its inherently robust randomized scheme been proven in any ultrasound blood flow imaging methods. This study thus proposed to employ rSVD as a fast and robust clutter filter for ultrafast echocardiograms prior to power Doppler analysis. Ultrafast echocardiograms of nine normal human hearts were acquired in vivo by our cascaded synthetic aperture imaging method. One subject was additionally scanned under four different sonographic signal-to-noise ratio (SNR) levels. Contrast ratio (CR) and contrast-to-noise ratio (CNR) of in vivo power Doppler images obtained from filtered ultrafast echocardiograms were calculated, and their mean and standard deviation within a cardiac cycle represented temporal average and variation of contrast resolution, respectively. Our in vivo results showed that rSVD accelerated clutter filtering by 12-fold and provided significantly better local contrast (mean CNR values: p0.001) while being equally effective (mean CR values: p = 0.20) compared with full-SVD. rSVD yielded smaller standard deviations of CR (1.32 dB vs. 5.49 dB) and CNR (1.27 dB vs. 5.49 dB) than full-SVD in the lowest SNR scenario, thus substantiating its superior robustness. Our findings suggest using rSVD in ultrafast echocardiographic blood dynamics analysis.

Background Strategies to improve long‐term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. Methods and Results In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end‐stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1‐year median follow‐up, mild and severe groups incurred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40–7.17] and HR, 9.30 [95% CI, 4.09–21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14–9.52] and subdistribution HR, 9.29 [95% CI, 3.09–27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25–3.55] and subdistribution HR, 3.55 [95% CI, 2.04–6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25–3.55] and HR, 3.55 [95% CI, 2.04–6.16]). Modified model for end‐stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P P =0.004) for all‐cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without. Conclusions Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery.

Background The characteristics of infective endocarditis (IE) in Asians are poorly understood. Therefore, we aim to describe the epidemiological trends and clinical features of IE in Hong Kong.Methods All patients with incident IE from 2002-2019 in a territory-wide clinical database in Hong Kong were identified. We studied the age- and sex-adjusted and one-year mortality of IE between 2002 and 2019 and identified significant contributors to 1-year all-cause death using the attributable fraction. We used propensity score and inverse propensity of treatment weighting to study the association of surgery with mortality.Findings A total of 5139 patients (60.4 +/- 18.2 years, 37% women) were included. The overall incidence of IE was 4.9 per 100,000 person-year, which did not change over time (P = 0.17). Patients in 2019 were older and more comorbid than those in 2002. The one-year crude mortality rate was 30% in 2002, which did not change significantly over time (P = 0.10). Between 2002 and 2019, the rate of surgery increased and was associated with a 51% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.49 [0.28-0.87], P = 0.015). Advanced age (attributable fraction 19%) and comorbidities (attributable fraction 15%) were significant contributors to death.Interpretation The incidence of IE in Hong Kong did not change between 2002 and 2019. Patients with IE in 2019 were older and had more comorbidities than those in 2002. Mortality of IE remains persistently high in Hong Kong. Together, these data can guide public health strategies to improve the outcomes of patients with IE. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.

Tricuspid regurgitation (TR) is a well-known complication after permanent pacemaker implantation. The aim of this study was to compare the degree of TR and the relationship of lead position across the tricuspid valve (TV) between patients with right ventricular apical (RVA) and non-RVA pacing determined by three-dimensional echocardiography.Conventional and three-dimensional echocardiography was performed in 284 patients to determine the change in TR severity following permanent pacemaker implantation. Transvenous lead locations were based on fluoroscopic images. This was a retrospective study, and the selected pacing mode was not randomized.RVA pacing had more frequent severe TR (37.9% vs 25.7%, P = .03) compared with non-RVA pacing. Severe TR occurred in 9.7%, 12.6%, and 58.8% of patients when the lead passed through the middle, between the commissures, and impinging the TV leaflets, respectively. Non-RVA leads were more likely to be positioned in the middle of the TV (30.3% vs 12.1%, P .01) and had the lowest chance of leaflet impingement (33.6% vs 51.5%, P .01) compared with RVA leads. RVA pacing was associated with worsening of grade ≥2 TR severity compared with non-RVA pacing (42.4% vs 27.6%, P .01). A TV lead passage angle of -15° to 15° minimized TR.Pacing-induced TR is more prevalent with RVA than non-RVA pacing. Preferential lead impingement on the TV leaflet, as determined by TV lead passage angle, can explain the development and progression of pacing-induced TR.

Patients with axial spondyloarthritis (SpA) are subjected to elevated cardiovascular risks, but assessment of early myocardial damage and clinical risk stratification remained obscure. The aim of this study was to evaluate the prognostic value of speckle-tracking strain analysis and serum high-sensitivity troponin I (hsTnI) in patients with axial SpA. Two-dimensional speckle-tracking echocardiography was performed to derive longitudinal strain (LS), circumferential strain (CS), and radial strain (RS). Serum hsTnI was measured by validated immunoassay (Architect i1000SR Abbott) as indicator of subclinical myocardial damage. The mean Bath Ankylosing Spondylitis Disease Activity Index and median modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were 3.8 and 15.5, respectively. Over a median follow-up of 81 months, major adverse cardiovascular events (MACE) occurred in 13% of subjects (n = 116). Univariate Cox regression showed that age, disease duration, Bath Ankylosing Spondylitis Functional Index, modified Schober test, mSASSS, hsTnI, interventricular septal thickness, E/E′, LS, RS, and carotid intima-media thickness were significant predictors of MACE (all P

Aims Long-term risk stratification and surgical timing remain suboptimal in concomitant aortic and mitral (double) valve surgery. This study sought to examine the predictors, changes, and prognostic implications of right ventricular (RV) remodelling in patients undergoing double-valve surgery. Methods and results In 152 patients undergoing double-valve surgery, four RV remodelling patterns were characterized using transthoracic echocardiography: normal RV size and systolic function (Pattern 1); dilated RV (tricuspid annulus diameter >35 mm) with normal systolic function (Pattern 2); normal RV size with systolic dysfunction (percentage RV fractional area change Conclusion Right ventricular remodelling was strongly related to adverse outcomes and deserves consideration as part of the risk and decision-making algorithms in double-valve surgery.

BackgroundThe presence of tricuspid regurgitation (TR) is very common in patients with concomitant left-sided valve disease. Recent studies have advocated an additional grading of massive TR that is beyond severe. The present study sought to characterize the spectrum of TR in patients undergoing tricuspid annuloplasty (TA) and to evaluate the prognostic value of TR severity for post-operative outcome following TA.MethodsA total of 176 patients who underwent TA with combined left-sided valve surgery, secondary to rheumatic valvular heart disease, were prospectively evaluated. The severity of TR was quantified by effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were categorized as having non-massive TR (EROA < 0.6 cm2) or massive TR (EROA ≥ 0.6 cm2). Adverse outcome was defined as all-cause mortality or heart failure requiring hospital admission following TA.ResultsA total of 55 (31%) patients were considered to have massive TR. Patients with massive TR had a greater right ventricular dimension but a smaller left ventricular dimension compared with those with non-massive TR. After a median follow-up of 39 months, 35 adverse events occurred. Cox-regression analysis showed that both continuous EROA and dichotomized EROA (massive vs. non-massive TR) were independently associated with adverse events even after multivariable adjustment. Further, Harrell C index demonstrated that the addition of massive TR provided better discrimination ability of a prediction model to known prognosticators following TA.ConclusionsMassive TR is common and up to 31% of study population had massive TR. Massive TR was associated with adverse outcome in patients undergoing TA. Classification of the severity of TR by quantitative measures and identification of massive TR in patients with concomitant left-sided valve disease are essential when considering the optimal timing of corrective surgery.

Background Evidence suggests that chronic obstructive pulmonary disease (COPD) is associated with a higher risk of lung carcinoma. Using a territory-wide clinical electronic medical records system, we investigated the association between low-dose aspirin use (≤160 mg) among patients with COPD and incidence of lung carcinoma and the corresponding risk of bleeding. Methods and findings This is a retrospective cohort study conducted utilizing Clinical Data Analysis Reporting System (CDARS), a territory-wide database developed by the Hong Kong Hospital Authority. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between aspirin nonusers (35,049 patients) with new aspirin users (7,679 patients) among all eligible COPD patients from 2005 to 2018 attending any public hospitals. The median age of the cohort was 75.7 years (SD = 11.5), and 80.3% were male. Competing risk regression with Cox proportional hazards model were performed to estimate the subdistribution hazard ratio (SHR) of lung carcinoma with low-dose aspirin and the associated bleeding events. Of all eligible patients, 1,779 (4.2%, 1,526 and 253 among nonusers and users) were diagnosed with lung carcinoma over a median follow-up period of 2.6 years (interquartile range [IQR]: 1.4 to 4.8). Aspirin use was associated with a 25% lower risk of lung carcinoma (SHR = 0.75, 95% confidence interval [CI] 0.65 to 0.87, p =, In a cohort study, Si-Yeung Yu and colleagues investigate the association between low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong., Author summary Why was this study done? Lung carcinoma is the most common malignancy worldwide, and chronic obstructive pulmonary disease (COPD), for which no curative treatments exist, is a prevalent risk factor of lung carcinoma. Aspirin is a medication with potential anticancer effects. Its effect on lung cancer, however, remains controversial. To our knowledge, its effect in patients in COPD remains unstudied. Aspirin is also known to cause bleeding. However, its effects in COPD patients, again to our knowledge, also remains unstudied. What did the researchers do and find? Using a territory-wide database, the risk of lung carcinoma was assessed in patients with COPD defined as aspirin nonusers (35,049) and aspirin users (7,679 patients). A mathematical model was used, which balances the 2 cohorts by their comorbidities, drug uses, demographic variables, and proxy variables for their socioeconomic status. Aspirin use was associated with a 25% lower risk of lung carcinoma, implying that within our cohort, every 125 patients treated for 5 years is associated with one fewer case of lung carcinoma. We found, additionally, that aspirin use was associated with an increased risk of coughing up blood, although the overall risk of gastrointestinal bleeding is not increased. What do these findings mean? Aspirin may be implicated as a potential preventative treatment for lung carcinoma in COPD patients, but the increased risk of adverse effects merits further evaluation. The current study design was unable to eliminate the possibility that aspirin users were more likely to seek additional treatment, although this is mitigated through design choices in developing the mathematical model. The observational nature of the study prevents causality from being established. The use of aspirin in COPD should depend on the benefits and harms associated with its usage, when they have been thoroughly studied in randomized trials.

Myocardial infarction arises from an excessive or prolonged inflammatory response, leading to ventricular remodeling or impaired cardiac function. Macrophages exhibit different polarization types associated with inflammation both at steady state and after myocardial infarction. Exosomal miR-146a-5p has been identified as an important molecule in the cardiovascular field in recent years. However, the effect of cardiomyocyte-derived exosomal miR-146a-5p on macrophages has not yet been elucidated. Initially, we found that exosomes with low expression of miR-146a-5p derived from myocardial infarction tissues modulated macrophage polarization. To determine whether cardiomyocyte-derived exosomal miR-146a-5p mediated macrophage polarization, we treated macrophages with exosomes rich in miR-146a-5p collected from neonatal mouse cardiomyocytes. The effects of exosomal miR-146a-5p on macrophage polarization were measured using RT-qPCR, transwell assays, and western blotting. The results showed that the increased expression of miR-146a-5p promoted M1 macrophage polarization, inhibited M2 macrophage polarization, and increased the expression of VEGFA. However, the decreased expression of exosomalmiR-146a-5p showed the opposite trends. Interestingly, in contrast to treatment with the solitary miR-146a-5p mimic, exosomal miR-146a-5p derived from neonatal mouse cardiomyocytes reduced TNFα and iNOS expression. In addition, when macrophages were activated by the miR-146a-5p mimic or exosomal miR-146a-5p, the expression of TNF receptor-associated factor 6 (TRAF6), a target gene of miR-146a-5p, was reduced significantly. Taken together, these findings indicate that exosomal miR-146a-5p derived from cardiomyocytes could stimulate M1 macrophage polarization to induce an inflammatory reaction, while targeting TRAF6, exerting an anti-inflammatory effect. Exosomal miR-146a-5p plays important roles in macrophages, illuminating a novel potential therapeutic target in myocardial infarction.

COVID-19 vaccines are important for patients with heart failure (HF) to prevent severe outcomes but the safety concerns could lead to vaccine hesitancy. This study aimed to investigate the safety of two COVID-19 vaccines, BNT162b2 and CoronaVac, in patients with HF.We conducted a self-controlled case series analysis using the data from the Hong Kong Hospital Authority and the Department of Health. The primary outcome was hospitalization for HF and the secondary outcomes were major adverse cardiovascular events (MACE) and all hospitalization. We identified patients with a history of HF before February 23, 2021 and developed the outcome event between February 23, 2021 and March 31, 2022 in Hong Kong. Incidence rate ratios (IRR) were estimated using conditional Poisson regression to evaluate the risks following the first three doses of BNT162b2 or CoronaVac.We identified 32,490 patients with HF, of which 3035 were vaccinated and had a hospitalization for HF during the observation period (BNT162b2 = 755; CoronaVac = 2280). There were no increased risks during the 0-13 days (IRR 0.64 [95% confidence interval 0.33-1.26]; 0.94 [0.50-1.78]; 0.82 [0.17-3.98]) and 14-27 days (0.73 [0.35-1.52]; 0.95 [0.49-1.84]; 0.60 [0.06-5.76]) after the first, second and third doses of BNT162b2. No increased risks were observed for CoronaVac during the 0-13 days (IRR 0.60 [0.41-0.88]; 0.71 [0.45-1.12]; 1.64 [0.40-6.77]) and 14-27 days (0.91 [0.63-1.32]; 0.79 [0.46-1.35]; 1.71 [0.44-6.62]) after the first, second and third doses. We also found no increased risk of MACE or all hospitalization after vaccination.Our results showed no increased risk of hospitalization for HF, MACE or all hospitalization after receiving BNT162b2 or CoronaVac vaccines in patients with HF.The project was funded by a Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). F.T.T.L. (Francisco T.T. Lai) and I.C.K.W. (Ian C.K. Wong)'s posts were partly funded by the D24H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission.

Introduction: Increasing number of heart failure (HF) patients diagnosed with dementia due to improved treatment and aging population. Data relating to the association of statin use on the risk of dementia incidence among patients with HF are sparse. Hypothesis: The use of statin is associated with lower risk of new- onset dementia in HF population. Methods: Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (N=241,995) from 1996 to 2019. Propensity score matching was used to balance baseline covariates between statin nonusers (167,738 patients) with statin users (74,257 patients). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of incident dementia associated with statin use. Results: Of all eligible subjects, the mean age was 76.5±13.0 years, 115,371(47.7%) was male. Over a median follow-up of 2.7 years (interquartile range [IQR]: 0.6 to 6.7), 13,482 (5.6%) patients were diagnosed with dementia including Alzheimer's disease (N=5,253), senile dementia uncomplicated (N=4,273), arteriosclerotic dementia (N=3,262), and others (N=694). Statin use (vs. none) was associated with a 58% lower risk of dementia incidence (multivariable-adjusted sub-distribution hazard ratio [SHR]=0.42; 95% Confidence Interval [CI], 0.38 to 0.46) after accounting for death as a competing risk. Moreover, the male gender was associated with a 51% lower risk of dementia incidence (multivariable-adjusted SHR=0.59; 95%CI (0.54-0.65) compared with females. Conclusions: Our study suggests that there is substantial sex difference in the incidence of dementia among HF patients. Moreover, statin use is associated with a significantly lower risk of incident dementia in HF.

Introduction: Computational pressure-flow dynamics derived fractional flow reserve (caFFR) is an angiographic-derived index to determine the fractional flow reserve (FFR) in patients with stable coronary artery disease (CAD), without the need of invasive pressure wire and hyperaemic stimulus in FFR. Although the safety of FFR-guided deferral of revascularization in non-ischemic lesions is well-established, clinical events still occur. The aim of the study is to investigate the prognostic implications of caFFR in those without significant ischemia. Methods: 513 stable CAD patients (mean age=64.3±11.1, 57.7% male) with all lesions being nonischemic, defined by caFFR>0.75, without undergoing revascularization were recruited. The study population was divided into high (n=240) and low (n=273) caFFR groups, according to the median value of caFFR (0.89). The primary endpoint was 3-year major adverse cardiac events (MACE), defined as a composite of all-cause mortality, myocardial infarction (MI), target vessel revascularization (TVR) and hospitalization for heart failure. Results: A total of 44 composite events occurred, including 17 all-cause mortality, 2 MI, 8 TVR and 17 hospitalization for heart failure. Following multivariate adjustment, patients in low caFFR group had a significantly higher risk of MACE than those in high caFFR group (adjusted hazard ratio [HR], 3.02; 95% confidence interval [Cl], 1.19-7.71; P=0.02). Every 0.01 decrease in caFFR was associated with a higher risk of MACE (adjusted HR, 1.12; 95%Cl, 1.03-1.21; P Conclusions: In stable CAD patients without significant functional ischemia, caFFR provides valuable prognostic information on adverse cardiac outcomes. This novel index could enhance risk stratification in stable CAD patients with nonischemic lesions.

Introduction: Computational pressure-flow dynamics derived fractional flow reserve (caFFR) has emerged for non-invasive assessment of fractional flow reserve (FFR) in patients with stable coronary artery disease (CAD), without the need for hyperaemic induction and guidewire placement in conventional FFR. The clinical value of caFFR in diabetic patients, who are at risk of microvascular dysfunction, has not been validated. The aim of the study is to evaluate the use of caFFR in diabetic patients with stable CAD. Methods: A total of 212 stable CAD patients with diabetes (mean age=67.6±10.6, 66.5% male) were included. Patients were said to be adherent to caFFR if all ischemic vessels, defined by caFFR≤0.8 were treated with PCI and all nonischemic vessels, defined by caFFR>0.8 were not. Otherwise, they were considered to be non-adherent to caFFR. The primary endpoint was 3-year major adverse cardiac events (MACE), defined as a composite of cardiovascular mortality, non-fatal myocardial infarction (MI), stroke and unplanned revascularization. Results: Among the 212 patients, PCI was performed in 62.3% of them. A total of 26 composite events occurred, including 5 cardiovascular mortality, 5 non-fatal MI, 2 strokes and 14 unplanned revascularization. The incidence rate of MACE was significantly lower in adherent patients than in non-adherent patients (5.4% vs 15.8%; P=0.01). After multivariate adjustment, adherent patients had a significantly lower risk of MACE than non-adherent patients (adjusted hazard ratio [HR], 0.33; 95% confidence interval [Cl], 0.13-0.83; P=0.02). Conclusions: In stable CAD patients with diabetes, caFFR-guided revascularization significantly reduces the risk of MACE in 3 years. The findings support the potential use of caFFR in treatment guidance of diabetic patients.

Introduction Multiple valvular heart disease, a combination of stenotic and regurgitant lesions occurring on two or more valves, is a highly prevalent condition. For these patients, surgical correction is the only definitive treatment to improve prognosis, yet concomitant aortic and mitral (double) valve surgery is associated with poor post-operative outcomes. While current guidelines outline left ventricular dimensions and function as surgical triggers, little is known regarding the importance of right ventricular (RV) remodelling in these patients. Purpose We sought to evaluate the prognostic value of RV remodelling in patients undergoing double valve surgery. Methods RV remodelling was characterised by transthoracic echocardiography in 152 patients undergoing concomitant aortic and mitral valve replacement (n=118) or aortic valve replacement and mitral valve repair (n=34). Four patterns of RV remodelling were defined according to the presence of RV dilation (tricuspid annulus diameter>35mm) and RV systolic dysfunction (percentage RV fractional area change Results Overall, 62 (41%), 31 (20%), 35 (23%), and 24 (16%) patients were classified as RV remodelling patterns 1, 2, 3, and 4, respectively. Patients with advanced RV remodelling patterns were more frequently male, had worse renal function, and a higher EuroSCORE II. During a median follow-up of 43 months, 41 adverse events (22 heart failure hospitalisation and 19 deaths) occurred. Patients with patterns 3 and 4 RV remodelling had an increased risk of adverse events compared to pattern 1 (log-rank χ2 27.42; p Conclusion In patients with concomitant aortic and mitral valve disease, RV remodelling is frequent and associated with poorer outcomes. Our study highlights the involvement of the RV in left-sided valvular heart disease and underlines the importance of preoperative assessment of RV geometry and function in patients undergoing double valve surgery. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Infective endocarditis (IE) is associated with high mortality and complex microbiological profile. The antibiotic prophylaxis guidelines underwent a major revision in 2009 to reduce unnecessary antibiotic exposure. Substantial geographic variations in microbiological profiles exist, of which the understanding in an Asian population is lacking. Purpose We aim to describe the trends in the microbiology of IE in Hong Kong in the past 2 decades. Methods All patients aged 20 or above diagnosed with incident IE with blood culture results from 2000–2019 were included from a well-validated territory-wide database in Hong Kong, and were classified as 7 groups of causative organisms as shown in Figure 1. To evaluate the association between microbiology and 1-year all-cause death, a multivariable Cox proportional-hazards model was used, adjusted with demographics and comorbidities. Temporal trends in the proportion of each organism were characterised using Poisson regression. Interrupted time series analysis was used to evaluate the change in the organism-specific incidence after the revision of guidelines. Results In a total of 5,657 patients (age 59.9±18.3 years, 37.2% females), there were 2,185 (38.6%) patients with culture-negative endocarditis. Staphylococcus aureus (22.4%) and Streptococci (20.5%) were the most common organisms identified. Over time, there was a significant reduction in the proportion of culture-negative endocarditis (annual percentage change [APC] −2.3% [−2.8 to −1.7], P0.05). Compared to patients with culture-negative endocarditis, those infected with Staphylococcus aureus (hazard ratio [HR] 2.19 [1.94–2.47], P There was a significant increase in the proportion of methicillin-resistant Staphylococcus aureus (MRSA) endocarditis (APC 4.1% [1.9 to 6.3], P Conclusions Different causative organisms carry variable mortality signals in infective endocarditis. Over time, there were fewer cases of culture-negative endocarditis, and the revision of antibiotic prophylaxis guidelines did not result in a significant change in the microbiological profile. There was an increasing trend for MRSA endocarditis, which was associated with a higher risk of death. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Shenzhen Key Medical DisciplineThe Sanming Project of HKU-SZH Cardiology