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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 ([less than or equal to]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 = Conclusions In this study, we observed that low-dose aspirin use was associated with a lower risk of lung carcinoma and lung carcinoma-related mortality among COPD patients. While aspirin was not associated with an increased risk of UGIB, the risk of hemoptysis was elevated., Author(s): Si-Yeung Yu 1,2, Mary Sau-Man Ip 2, Xue Li 2, Ka-Shing Cheung 2, Qing-Wen Ren 2, Mei-Zhen Wu 2, Hang-Long Li 2, Pui-Fai Wong 2, Hung-Fat Tse 2, Kai-Hang [...]

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 <35%; Pattern 3); and dilated RV with systolic dysfunction (Pattern 4). The primary endpoint was the composite of heart failure hospitalization and all-cause mortality. Patterns 1, 2, 3, and 4 RV remodelling were present in 41, 20, 23, and 16% of patients, respectively. Patients with Stage 4 RV remodelling had worse renal function, higher EuroSCORE II, and impaired left ventricular ejection fraction. During a 3.7-year median follow up, 45 adverse events occurred. Patterns 3 and 4 RV remodelling were associated with significantly higher adverse event rates compared with Pattern 1 (37 and 75% vs. 11%, P < 0.01) and had incremental prognostic value when added to clinical parameters and EuroSCORE II (χ2 increased from 30 to 66, P < 0.01). At 1 year after surgery (n = 100), Patterns 3 and 4 RV remodelling had a higher risk of adverse events compared with Pattern 1. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims  Patients with heart failure (HF) have an increased risk of incident cancer. Data relating to the association of statin use with cancer risk and cancer-related mortality among patients with HF are sparse. Methods and results  Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (n  = 87 102) from 2003 to 2015. Inverse probability of treatment weighting was used to balance baseline covariates between statin nonusers (n  = 50 926) with statin users (n  = 36 176). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of cancer and cancer-related mortality associated with statin use. Of all eligible subjects, the mean age was 76.5 ± 12.8 years, and 47.8% was male. Over a median follow-up of 4.1 years (interquartile range: 1.6–6.8), 11 052 (12.7%) were diagnosed with cancer. Statin use (vs. none) was associated with a 16% lower risk of cancer incidence [multivariable adjusted subdistribution hazard ratio (SHR) = 0.84; 95% confidence interval (CI), 0.80–0.89]. This inverse association with risk of cancer was duration dependent; as compared with short-term statin use (3 months to <2 years), the adjusted SHR was 0.99 (95% CI, 0.87–1.13) for 2 to <4 years of use, 0.82 (95% CI, 0.70–0.97) for 4 to <6 years of use, and 0.78 (95% CI, 0.65–0.93) for ≥6 years of use. Ten-year cancer-related mortality was 3.8% among statin users and 5.2% among nonusers (absolute risk difference, −1.4 percentage points [95% CI, −1.6% to −1.2%]; adjusted SHR = 0.74; 95% CI, 0.67–0.81). Conclusion  Our study suggests that statin use is associated with a significantly lower risk of incident cancer and cancer-related mortality in HF, an association that appears to be duration dependent. [ABSTRACT FROM AUTHOR]

Background: Risk stratification of patients with symptomatic nonobstructive coronary artery disease remains uncertain. Our study assessed the clinical value of single-vessel, multivessel, and 3-vessel computational angiography-derived fractional flow reserve (caFFR) measurement in patients with nonobstructive coronary artery disease., Methods and Results: We enrolled patients with ≤50% stenosis with a caFFR value ≥0.8 in all 3 coronary arteries on coronary angiography. The sum of caFFR values in the 3 vessels was computed for each patient. Patient stratification was based on the median value of the following criteria: single-vessel analysis, multivessel analysis, and 3-vessel analysis. The primary end point of this study was major adverse cardiac events at 5 years, defined as a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. A total of 490 patients were included. The 5-year major adverse cardiac event rates in single-vessel analysis were statistically insignificant between low- and high-caFFR groups (left anterior descending artery [ P =0.163]; left circumflex artery [ P =0.797]; right coronary artery [ P =0.127]). In multivessel analysis, patients in the multiple-vessel low-caFFR group (with 2-3 vessels lower than median value of all coronary arteries) showed an increased risk of 5-year major adverse cardiac events compared with patients in the single-vessel low-caFFR group (0-1 vessel) (hazard ratio [HR], 2.648 [95% CI, 1.141-6.145]; P =0.023). In 3-vessel analysis, patients in the low 3-vessel caFFR group demonstrated a greater 5-year major adverse cardiac event risk than the high 3-vessel caFFR group (HR, 2.43 [95% CI, 1.087-5.433]; P =0.031)., Conclusions: We demonstrated that both multiple-vessel and 3-vessel caFFR measurements serve as valuable prognostic indicators for risk assessment in patients with nonobstructive coronary artery disease.

Background: Whether statin use can reduce the risk of heart failure (HF) remains controversial. The present study evaluates the association between statin use and HF in patients with atrial fibrillation., Methods and Results: Patients with newly diagnosed atrial fibrillation from 2010 to 2018 were included. An inverse probability of treatment weighting was used to balance baseline covariates between statin users (n=23 239) and statin nonusers (n=29 251). The primary outcome was incident HF. Cox proportional hazard models with competing risk regression were used to evaluate the risk of HF between statin users and nonusers. The median age of the cohort was 74.7 years, and 47.3% were women. Over a median follow-up of 5.1 years, incident HF occurred in 3673 (15.8%) statin users and 5595 (19.1%) statin nonusers. Statin use was associated with a 19% lower risk of HF (adjusted subdistribution hazard ratio, 0.81 [95% CI, 0.78-0.85]). Restricted to the statin users, duration of statin use was measured during follow-up; compared with short-term use (3 months to <2 years), there was a stepwise reduction in the risk of incident HF among those with 2 to <4 years of statin use (subdistribution hazard ratio, 0.86 [95% CI, 0.84-0.88]), 4 to <6 years of statin use (subdistribution hazard ratio, 0.74 [95% CI, 0.72-0.76]), and ≥6 years of statin use (subdistribution hazard ratio, 0.71 [95% CI, 0.69-0.74]). Subgroup analysis showed consistent reductions in the risk of HF with statin use., Conclusions: Statin use was associated with a decreased risk of incident HF in a duration-dependent manner among patients with atrial fibrillation.

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 <35%; Pattern 3); and dilated RV with systolic dysfunction (Pattern 4). The primary endpoint was the composite of heart failure hospitalization and all-cause mortality. Patterns 1, 2, 3, and 4 RV remodelling were present in 41, 20, 23, and 16% of patients, respectively. Patients with Stage 4 RV remodelling had worse renal function, higher EuroSCORE II, and impaired left ventricular ejection fraction. During a 3.7-year median follow up, 45 adverse events occurred. Patterns 3 and 4 RV remodelling were associated with significantly higher adverse event rates compared with Pattern 1 (37 and 75% vs. 11%, P < 0.01) and had incremental prognostic value when added to clinical parameters and EuroSCORE II (χ2 increased from 30 to 66, P < 0.01). At 1 year after surgery (n = 100), Patterns 3 and 4 RV remodelling had a higher risk of adverse events compared with Pattern 1., 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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Conflict of Interest: C.S.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Abbott, Actelion, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd., Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder & non-executive director of Us2.ai. All other authors report no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

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 <0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, 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.