Prediabetes is associated with increased cardiac events in patients with cancer who are prescribed anthracyclines.

BACKGROUND: Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. METHODS: The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. RESULTS: Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. CONCLUSIONS: In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. PLAIN LANGUAGE SUMMARY: Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.

Chronic kidney disease begets heart failure and vice versa: temporal associations between heart failure events in relation to incident chronic kidney disease in type 2 diabetes.

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.

Low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong: A cohort study.

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 = <0.001) and 26% decrease in lung carcinoma-related mortality (SHR = 0.74, 95% CI 0.64 to 0.86, p = <0.001). Subgroup analysis revealed that aspirin was beneficial for patients aged above or below 75 years, but was also beneficial among populations who were male, nondiabetic, and nonhypertensive. Aspirin use was not associated with an increased risk of upper gastrointestinal bleeding (UGIB) (SHR = 1.19, 95% CI 0.94 to 1.53, p = 0.16), but was associated with an increased risk of hemoptysis (SHR = 1.96, 95% CI 1.73 to 2.23, p < 0.001). The main limitations of the study were (i) that one group of patients may be more likely to seek additional medical attention, although this was partially mitigated by the use of propensity score analysis; and (ii) the observational nature of the study renders it unable to establish causality between aspirin use and lung carcinoma incidence. 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.

Statin associated lower cancer risk and related mortality in patients with heart failure.

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.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis.

BACKGROUND: Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD. METHODS: MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model. RESULTS: Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70-0.96), embolic stroke (RR 0.32, 95% CI 0.12-0.85), AF/AFL (RR 0.82, 95% CI 0.71-0.95), and VT (RR 0.73, 95% CI 0.53-0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58-1.17) and cardiac arrest (RR 0.83, 95% CI 0.61-1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used. CONCLUSIONS: SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.

Association of serum uric acid with biventricular myocardial dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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 m2, and glycated hemoglobin < or ≥7.0% (all P < 0.05). Multivariable linear regression analysis demonstrated that higher quartile of SUA was independently associated with impaired biventricular myocardial strain (all P < 0.05). CONCLUSIONS: SUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control.

Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study.

BACKGROUND: The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. METHODS: Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. RESULTS: The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e' (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (ß = 0.89, P < 0.01) and worsening of average E/e' (ß = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16-6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. CONCLUSION: Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

Statins and risks of dementia among patients with heart failure: a population-based retrospective cohort study in Hong Kong.

Background: Heart failure (HF) and dementia frequently co-exist with shared pathological mechanisms and risk factors. Our study aims to investigate the association between statin therapy and the risks of dementia and its subtypes among patients with HF. Methods: The Hong Kong Clinical Data Analysis and Reporting System database was interrogated to identify patients with incident HF diagnosis from 2004 to 2018, using ICD 9/ICD 10 codes. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between statin users (N = 54,004) and non-users (N = 50,291). The primary outcomes were incident all-cause dementia, including subtypes of Alzheimer's disease, vascular dementia, and unspecified dementia. Cox proportional-hazard model with competing risk regression was performed to estimate the sub-distribution hazards ratio (SHR) with corresponding 95% confidence intervals (CI) of the risks of all-cause dementia and its subtypes that are associated with statin use. Findings: Of all eligible patients with HF (N = 104,295), the mean age was 74.2 ± 13.6 years old and 52,511 (50.3%) were male. Over a median follow-up of 9.9 years (interquartile range [IQR]: 6.4-13.0), 10,031 (9.6%) patients were diagnosed with dementia, among which Alzheimer's disease (N = 2250), vascular dementia (N = 1831), and unspecified dementia (N = 5950) were quantified separately. After IPTW, statin use was associated with a 20% lower risk of incident dementia compared with non-use (multivariable-adjusted SHR 0.80, 95% CI 0.76-0.84). Stratified by subtypes of dementia, statin use was associated with a 28% lower risk of Alzheimer's disease (SHR 0.72, 95% CI 0.63-0.82), 18% lower risk of vascular dementia (SHR 0.82, 95% CI 0.70-0.95), and a 20% lower risk of unspecified dementia (SHR 0.80, 95% CI 0.75-0.85). Interpretation: In patients with HF, statin use was associated with a significantly lower risk of all-cause dementia and its subtypes, including Alzheimer's disease, vascular dementia, and unspecified dementia. Both randomized trials and experimental studies to validate the potential neuroprotective effect of statin are warranted. Funding: No funding was provided for this study.

Target organ damage in untreated hypertensive patients with primary aldosteronism.

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.

Risk of hyperkalaemia in patients with type 2 diabetes mellitus prescribed with SGLT2 versus DPP-4 inhibitors.

AIMS: To investigate the risk of hyperkalaemia in new users of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5 mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28 599 patients (mean age 60 ± 11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10 586 were new users of SGLT2 inhibitors and 18 013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71-0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67-0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81-1.01). CONCLUSION: Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.

Glycated Hemoglobin Variability Is Associated With Adverse Outcomes in Patients With Heart Failure Irrespective of Diabetic Status.

BACKGROUND: The effect of glycated hemoglobin (HbA1c) variability on adverse outcomes in patients with heart failure (HF) is unclear. We aim to investigate the predictive value of HbA1c variability on the risks of all-cause death and HF rehospitalization in patients with HF irrespective of their diabetic status. METHODS AND RESULTS: Using a previously validated territory-wide clinical data registry, HbA1c variability was assessed by average successive variability (ASV) or SD of all HbA1c measurements after HF diagnosis. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and its corresponding 95% CI. A total of 65 950 patients with HF were included in the study. Over a median follow-up of 6.7 (interquartile range, 4.0-10.6) years, 34 508 patients died and 52 446 required HF rehospitalization. Every unit increment of variability in HbA1c was significantly associated with higher HF rehospitalization (HR ASV, 1.20 [95% CI, 1.18-1.23]) and all-cause death (HR ASV, 1.50 [95% CI, 1.47-1.53]). Diabetes significantly modified the association between HbA1c variability and outcomes (Pinteraction<0.001). HbA1c variability in patients with HF without diabetes conferred a higher risk of rehospitalization (HR ASV, 1.92 [95% CI, 1.70-2.17] versus HR ASV, 1.19 [95% CI, 1.17-1.21]), and all-cause death (HR ASV, 3.90 [95% CI, 3.31-4.61] versus HR ASV, 1.47 [95% CI, 1.43-1.50] compared with patients with diabetes). CONCLUSIONS: HbA1c variability is significantly associated with greater risk of rehospitalization and all-cause death in patients with HF, irrespective of their diabetic status. These observations were more pronounced in patients with HF without diabetes.

Morphological and functional types of tricuspid regurgitation: prognostic value in patients undergoing tricuspid annuloplasty during left-sided valvular surgery.

BACKGROUND: The nonuniform benefit of tricuspid annuloplasty may be explained by the proportionality of tricuspid regurgitation (TR) severity to right ventricular (RV) area. The purpose of this study was to delineate distinct morphological phenotypes of functional TR and investigate their prognostic implications in patients undergoing tricuspid annuloplasty during left-sided valvular surgery. METHODS: The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area (RVDA) were retrospectively assessed in 290 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from penalized splines and maximally selected rank statistics, patients were stratified into proportionate (EROA/RVDA ratio ≤ 1.74) and disproportionate TR (EROA/RVDA ratio > 1.74). RESULTS: Overall, 59 (20%) and 231 (80%) patients had proportionate and disproportionate TR, respectively. Compared to those with proportionate TR, patients with disproportionate TR were older, had a higher prevalence of atrial fibrillation, lower pulmonary pressures, more impaired RV function, and larger tricuspid leaflet tenting area. Over a median follow-up of 4.1 years, 79 adverse events (47 heart failure hospitalizations and 32 deaths) occurred. Patients with disproportionate TR had higher rates of adverse events than those with proportionate TR (32% vs 10%; P = 0.001) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based classification of TR severity in outcome prediction and provided incremental prognostic value to both the EuroSCORE II and STS score (incremental χ2 = 6.757 and 9.094 respectively; both P < 0.05). CONCLUSIONS: Disproportionate TR is strongly associated with adverse prognosis and may aid patient selection and risk stratification for tricuspid annuloplasty with left-sided valvular surgery.

Pre-admission and In-Hospital Statin Use is Associated With Reduced Short-Term Mortality in Infective Endocarditis.

OBJECTIVE: 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 AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prognostic value of right ventricular remodelling in patients undergoing concomitant aortic and mitral valve surgery.

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.

Prediabetes Is Associated With Increased Risk of Heart Failure Among Patients With Atrial Fibrillation.

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.

Clinical Value of Computational Angiography-derived Fractional Flow Reserve in Stable Coronary Artery Disease.

The utilization of FFR remains low. Our study evaluated the per-vessel prognostic value of computational pressure-flow dynamics-derived FFR (caFFR) among patients with stable coronary artery disease. A total of 3329 vessels from 1308 patients were included and analysed. They were stratified into ischaemic (caFFR ≤ 0.8) and non-ischaemic (caFFR > 0.8) cohorts, and the associations between PCI and outcomes were evaluated. The third cohort comprised all included vessels, and the associations between treatment adherent-to-caFFR (PCI in vessels with caFFR ≤ 0.8 and no PCI in vessels with caFFR > 0.8) and outcomes were evaluated. The primary outcome was VOCE, defined as a composite of vessel-related cardiovascular mortality, non-fatal myocardial infarction, and repeat revascularization. PCI was associated with a lower 3-year risk of VOCE in the ischaemic cohort (HR, 0.44; 95% CI, 0.26-0.74; P = 0.002) but not in the non-ischaemic cohort. The risk of VOCE was lower in the adherent-to-caFFR group (n = 2649) (HR, 0.69; 95% CI, 0.48-0.98; P = 0.039). A novel index that uses coronary angiography images to estimate FFR may have substantial clinical value in guiding management among patients with stable coronary artery disease.

Statin Therapy Is Associated With a Lower Risk of Heart Failure in Patients With Atrial Fibrillation: A Population-Based Study.

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.

Incidence, Clinical Correlates, and Prognostic Impact of Dementia in Heart Failure: A Population-Based Cohort Study.

Background: Heart failure (HF) may increase the risk of dementia via shared risk factors. Objectives: The authors investigated the incidence, types, clinical correlates, and prognostic impact of dementia in a population-based cohort of patients with index HF. Methods: The previously territory-wide database was interrogated to identify eligible patients with HF (N = 202,121) from 1995 to 2018. Clinical correlates of incident dementia and their associations with all-cause mortality were assessed using multivariable Cox/competing risk regression models where appropriate. Results: Among a total cohort aged ≥18 years with HF (mean age 75.3 ± 13.0 years, 51.3% women, median follow-up 4.1 [IQR: 1.2-10.2] years), new-onset dementia occurred in 22,145 (11.0%), with age-standardized incidence rate of 1,297 (95% CI: 1,276-1,318) per 10,000 in women and 744 (723-765) per 10,000 in men. Types of dementia were Alzheimer's disease (26.8%), vascular dementia (18.1%), and unspecified dementia (55.1%). Independent predictors of dementia included: older age (≥75 years, subdistribution hazard ratio [SHR]: 2.22), female sex (SHR: 1.31), Parkinson's disease (SHR: 1.28), peripheral vascular disease (SHR: 1.46), stroke (SHR: 1.24), anemia (SHR: 1.11), and hypertension (SHR: 1.21). The population attributable risk was highest for age ≥75 years (17.4%) and female sex (10.2%). New-onset dementia was independently associated with increased risk of all-cause mortality (adjusted SHR: 4.51; P < 0.001). Conclusions: New-onset dementia affected more than 1 in 10 patients with index HF over the follow-up, and portended a worse prognosis in these patients. Older women were at highest risk and should be targeted for screening and preventive strategies.

Intraventricular 4D flow cardiovascular magnetic resonance for assessing patients with heart failure with preserved ejection fraction: a pilot study.

Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging. Intraventricular four-dimensional flow (4D flow) phase-contrast cardiovascular magnetic resonance (CMR) can assess different components of left ventricular (LV) flow including direct flow, delayed ejection, retained inflow and residual volume. This could be utilised to identify HFpEF. This study investigated if intraventricular 4D flow CMR could differentiate HFpEF patients from non-HFpEF and asymptomatic controls. Suspected HFpEF patients and asymptomatic controls were recruited prospectively. HFpEF patients were confirmed using European Society of Cardiology (ESC) 2021 expert recommendations. Non-HFpEF patients were diagnosed if suspected HFpEF patients did not fulfil ESC 2021 criteria. LV direct flow, delayed ejection, retained inflow and residual volume were obtained from 4D flow CMR images. Receiver operating characteristic (ROC) curves were plotted. 63 subjects (25 HFpEF patients, 22 non-HFpEF patients and 16 asymptomatic controls) were included in this study. 46% were male, mean age 69.8 ± 9.1 years. CMR 4D flow derived LV direct flow and residual volume could differentiate HFpEF vs combined group of non-HFpEF and asymptomatic controls (p < 0.001 for both) as well as HFpEF vs non-HFpEF patients (p = 0.021 and p = 0.005, respectively). Among the 4 parameters, direct flow had the largest area under curve (AUC) of 0.781 when comparing HFpEF vs combined group of non-HFpEF and asymptomatic controls, while residual volume had the largest AUC of 0.740 when comparing HFpEF and non-HFpEF patients. CMR 4D flow derived LV direct flow and residual volume show promise in differentiating HFpEF patients from non-HFpEF patients.