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.

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.

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.

Mortality in patients admitted to hospital with heart failure in China: a nationwide Cardiovascular Association Database-Heart Failure Centre Registry cohort study.

BACKGROUND: China has the largest burden of heart failure worldwide. However, large-scale studies on heart failure mortality are scarce. We aimed to investigate mortality and identify risk factors for mortality among patients with heart failure in China. METHODS: This prospective cohort study used data from the China Cardiovascular Association (CCA) Database-Heart Failure Centre Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. We included patients enrolled from Jan 1, 2017, to Dec 31, 2021, across 572 CCA Database-Heart Failure Centre certified hospitals in 31 provinces of mainland China. Eligible patients were aged 18 years or older (younger than 100 years) with a principal discharge diagnosis of heart failure based on Chinese heart failure guidelines. All-cause mortality at 30 days, 1 year, and 3 years for patients with heart failure were calculated and the causes of death were recorded. Multivariable analysis was used to analyse factors associated with all-cause mortality and cardiovascular mortality. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2200066305. FINDINGS: Of the 327 477 patients in the registry, 230 637 eligible adults with heart failure were included in our analyses. Participant mean age was 69·3 years (SD 13·2), 94 693 (41·1%) participants were female, and 135 944 (58·9%) were male. The median follow-up time was 531 days (IQR 251-883). Post-discharge all-cause mortality of patients with heart failure at 30 days was 2·4% (95% CI 2·3-2·5), at 1 year was 13·7% (13·5-13·9), and at 3 years was 28·2% (27·7-28·6). Cardiovascular death accounted for 32 906 (71·5%) of 46 006 all-cause deaths. Patients with heart failure with reduced ejection fraction had the highest all-cause mortality. A lower guideline adherence score was independently associated with the increase of all-cause and cardiovascular mortality. INTERPRETATION: In China, mortality for patients with heart failure is still high, especially in patients with reduced ejection fraction. Our findings suggest that guideline-directed medical therapy needs to be improved. FUNDING: National High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Prognostic Utility of Left Atrial Strain From MRI Feature Tracking in Ischemic and Nonischemic Dilated Cardiomyopathy: A Multicenter Study.

BACKGROUND. MRI-based prognostic evaluation in patients with dilated cardiomyopathy (DCM) has historically used markers of late gadolinium enhancement (LGE) and feature tracking (FT)-derived left ventricular global longitudinal strain (LVGLS). Early data indicate that FT-derived left atrial strain (LAS) parameters, including reservoir, conduit, and booster, may also have prognostic roles in such patients. OBJECTIVE. The purpose of our study was to evaluate the prognostic utility of LAS parameters, derived from MRI FT, in patients with ischemic or nonischemic DCM, including in comparison with the traditional parameters of LGE and LVGLS. METHODS. This retrospective study included 811 patients with ischemic or nonischemic DCM (median age, 60 years; 640 men, 171 women) who underwent cardiac MRI at any of five centers. FT-derived LAS parameters and LVGLS were measured using two- and four-chamber cine images. LGE percentage was quantified. Patients were assessed for a composite outcome of all-cause mortality or heart failure hospitalization. Multivariable Cox regression analyses including demographic characteristics, cardiovascular risk factors, medications used, and a wide range of cardiac MRI parameters were performed. Kaplan-Meier analyses with log-rank tests were also performed. RESULTS. A total of 419 patients experienced the composite outcome. Patients who did, versus those who did not, experience the composite outcome had larger LVGLS (-6.7% vs -8.3%, respectively; p < .001) as well as a smaller LAS reservoir (13.3% vs 19.3%, p < .001), LAS conduit (4.7% vs 8.0%, p < .001), and LAS booster (8.1% vs 10.3%, p < .001) but no significant difference in LGE (10.1% vs 11.3%, p = .51). In multivariable Cox regression analyses, significant independent predictors of the composite outcome included LAS reservoir (HR = 0.96, p < .001) and LAS conduit (HR = 0.91, p < .001). LAS booster and LGE were not significant independent predictors in the models. LVGLS was a significant independent predictor only in a model that initially included LAS booster but not the other LAS parameters. In Kaplan-Meier analysis, all three LAS parameters were significantly associated with the composite outcome (p < .001). CONCLUSION. In this multicenter study, LAS reservoir and LAS conduit were significant independent prognostic markers in patients with ischemic or nonischemic DCM, showing greater prognostic utility than the currently applied markers of LVGLS and LGE. CLINICAL IMPACT. FT-derived LAS analysis provides incremental prognostic information in patients with DCM.

Elevated ITGA1 levels in type 2 diabetes: implications for cardiac function impairment.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies. METHODS: Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals' left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF. RESULTS: Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p=0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF. CONCLUSIONS/INTERPRETATION: ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes. DATA AVAILABILITY: The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org .

Expert recommendations for the management of iron deficiency in patients with heart failure in Asia.

BACKGROUND: Iron deficiency is a common comorbidity in heart failure (HF) and is independently associated with a worse quality-of-life and exercise capacity, as well as increased risk of hospitalization, regardless of anemia status. Although international guidelines have provided recommendations for the management of iron deficiency in patients with HF, guidelines in Asia are less established, and practical use of guidelines for management of iron deficiency is limited in the region. METHODS: A panel comprising cardiologists from China, Hong Kong, India, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, and Thailand convened to share insights and provide guidance for the optimal management of iron deficiency in patients with HF, tailored for the Asian community. RESULTS: Expert opinions were provided for the screening, diagnosis, treatment and monitoring of iron deficiency in patients with HF. It was recommended that all patients with HF with reduced ejection fraction should be screened for iron deficiency, and iron-deficient patients should be treated with intravenous iron. Monitoring of iron levels in patients with HF should be carried out once or twice yearly. Barriers to the management of iron deficiency in patients with HF in the region include low awareness of iron deficiency amongst general physicians, lack of reimbursement for screening and treatment, and lack of proper facilities for administration of intravenous iron. CONCLUSIONS: These recommendations provide a structured approach to the management of iron deficiency in patients with HF in Asia.

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.

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.

Post-COVID-19 vaccination myocarditis: a prospective cohort study pre and post vaccination using cardiovascular magnetic resonance.

BACKGROUND: Concerns about COVID-19 vaccination induced myocarditis or subclinical myocarditis persists in some populations. Cardiac magnetic resonance imaging (CMR) has been used to detect signs of COVID-19 vaccination induced myocarditis. This study aims to: (i) characterise myocardial tissue, function, size before and after COVID-19 vaccination, (ii) determine if there is imaging evidence of subclinical myocardial inflammation or injury after vaccination using CMR. METHODS: Subjects aged ≥ 12yrs old without prior COVID-19 or COVID-19 vaccination underwent two CMR examinations: first, ≤ 14 days before the first COVID-19 vaccination and a second time ≤ 14 days after the second COVID-19 vaccination. Biventricular indices, ejection fraction (EF), global longitudinal strain (GLS), late gadolinium enhancement (LGE), left ventricular (LV) myocardial native T1, T2, extracellular volume (ECV) quantification, lactate dehydrogenase (LDH), white cell count (WCC), C-reactive protein (CRP), NT-proBNP, troponin-T, electrocardiogram (ECG), and 6-min walk test were assessed in a blinded fashion. RESULTS: 67 subjects were included. First and second CMR examinations were performed a median of 4 days before the first vaccination (interquartile range 1-8 days) and 5 days (interquartile range 3-6 days) after the second vaccination respectively. No significant change in global native T1, T2, ECV, LV EF, right ventricular EF, LV GLS, LGE, ECG, LDH, troponin-T and 6-min walk test was demonstrated after COVID-19 vaccination. There was a significant WCC decrease (6.51 ± 1.49 vs 5.98 ± 1.65, p = 0.003) and CRP increase (0.40 ± 0.22 vs 0.50 ± 0.29, p = 0.004). CONCLUSION: This study found no imaging, biochemical or ECG evidence of myocardial injury or inflammation post COVID-19 vaccination, thus providing some reassurance that COVID-19 vaccinations do not typically cause subclinical myocarditis.

miR-455-5p promotes pathological cardiac remodeling via suppression of PRMT1-mediated Notch signaling pathway.

Pathological cardiac remodeling plays an essential role in the progression of cardiovascular diseases, and numerous microRNAs have been reported to participate in pathological cardiac remodeling. However, the potential role of microRNA-455-5p (miR-455-5p) in this process remains to be elucidated. In the present study, we focused on clarifying the function and searching the direct target of miR-455-5p, as well as exploring its underlying mechanisms in pathological cardiac remodeling. We found that overexpression of miR-455-5p by transfection of miR-455-5p mimic in vitro or tail vain injection of miR-455-5p agomir in vivo provoked cardiac remodeling, whereas genetic knockdown of miR-455-5p attenuated the isoprenaline-induced cardiac remodeling. Besides, miR-455-5p directly targeted to 3'-untranslated region of protein arginine methyltransferase 1 (PRMT1) and subsequently downregulated PRMT1 level. Furthermore, we found that PRMT1 protected against cardiac hypertrophy and fibrosis in vitro. Mechanistically, miR-455-5p induced cardiac remodeling by downregulating PRMT1-induced asymmetric di-methylation on R1748, R1750, R1751 and R1752 of Notch1, resulting in suppression of recruitment of Presenilin, Notch1 cleavage, NICD releasing and Notch signaling pathway. Finally, circulating miR-455-5p was positively correlated with parameters of left ventricular wall thickening. Taken together, miR-455-5p plays a provocative role in cardiac remodeling via inactivation of the PRMT1-mediated Notch signaling pathway, suggesting miR-455-5p/PRMT1/Notch1 signaling axis as potential therapeutic targets for pathological cardiac remodeling.

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.

Gas station in blood vessels: An endothelium mimicking, self-sustainable nitric oxide fueling stent coating for prevention of thrombosis and restenosis.

Stenting is the primary treatment for vascular obstruction-related cardiovascular diseases, but it inevitably causes endothelial injury which may lead to severe thrombosis and restenosis. Maintaining nitric oxide (NO, a vasoactive mediator) production and grafting endothelial glycocalyx such as heparin (Hep) onto the surface of cardiovascular stents could effectively reconstruct the damaged endothelium. However, insufficient endogenous NO donors may impede NO catalytic generation and fail to sustain cardiovascular homeostasis. Here, a dopamine-copper (DA-Cu) network-based coating armed with NO precursor L-arginine (Arg) and Hep (DA-Cu-Arg-Hep) is prepared using an organic solvent-free dipping technique to form a nanometer-thin coating onto the cardiovascular stents. The DA-Cu network adheres tightly to the surface of stents and confers excellent NO catalytic activity in the presence of endogenous NO donors. The immobilized Arg functions as a NO fuel to generate NO via endothelial nitric oxide synthase (eNOS), while Hep works as eNOS booster to increase the level of eNOS to decompose Arg into NO, ensuring a sufficient supply of NO even when endogenous donors are insufficient. The synergistic interaction between Cu and Arg is analogous to a gas station to fuel NO production to compensate for the insufficient endogenous NO donor in vivo. Consequently, it promotes the reconstruction of natural endothelium, inhibits smooth muscle cell (SMC) migration, and suppresses cascading platelet adhesion, preventing stent thrombosis and restenosis. We anticipate that our DA-Cu-Arg-Hep coating will improve the quality of life of cardiovascular patients through improved surgical follow-up, increased safety, and decreased medication, as well as revitalize the stenting industry through durable designs.

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.

Habitual physical activity improves outcomes among patients with myocardial infarction.

Purpose: This study evaluates the association between habitual physical activity (HPA) and the outcomes of patients with myocardial infarction (MI). Methods: Patients newly diagnosed with MI were divided into two groups based on whether they engaged in HPA, defined as an aerobic activity with a duration of no less than 150 min/week, before the index admission. The primary outcomes included major adverse cardiovascular events (MACEs), cardiovascular (CV) mortality, and cardiac readmission rate 1 year following the index date of admission. A binary logistic regression model was applied to analyze whether HPA was independently associated with 1-year MACEs, 1-year CV mortality, and 1-year cardiac readmission rate. Results: Among the 1,266 patients (mean age 63.4 years, 72% male), 571 (45%) engaged in HPA, and 695 (55%) did not engage in HPA before MI. Patients who participated in HPA were independently associated with a lower Killip class upon admission (OR = 0.48: 95% CI, 0.32-0.71, p < 0.001) and a lower prevalence of 1-year MACEs (OR = 0.74: 95% CI, 0.56-0.98, p = 0.038) and 1-year CV mortality (OR = 0.50: 95% CI, 0.28-0.88, p = 0.017) than those who did not participate in HPA. HPA was not associated with cardiac-related readmission (OR = 0.87: 95% CI, 0.64-1.17, p = 0.35). Conclusions: HPA before MI was independently associated with a lower Killip class upon admission, 1-year MACEs, and 1-year CV mortality rate.

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.

Risk of ICU Admission and Related Mortality in Patients With Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors: A Territory-Wide Retrospective Cohort Study.

OBJECTIVES: The benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the occurrence rate of adverse cardiac and renal outcomes in patients with type 2 diabetes has been well described in randomized trials. Whether this benefit extends to patients at the most severe end of the disease spectrum requiring admission to the ICU remains to be examined. DESIGN: Retrospective observational study. SETTING: Data were obtained from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System). PATIENTS: All adult patients (age ≥ 18 yr) with type 2 diabetes and newly prescribed SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors between January 1, 2015, and December 31, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 1:2 propensity score matching, a total of 27,972 patients (10,308 SGLT2 inhibitors vs 17,664 DPP-4 inhibitors) were included in the final analysis. The mean age was 59 ± 11 years, and 17,416 (62.3%) were male. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with decreased ICU admission (286 [2.8%] vs 645 [3.7%]; hazard ratio [HR], 0.79; 95% CI, 0.69-0.91; p = 0.001) and lower risks of all-cause mortality (315 [3.1%] vs 1,327 [7.5%]; HR, 0.44; 95% CI, 0.38-0.49; p < 0.001), compared with DPP-4 inhibitors. The severity of illness upon ICU admission by Acute Physiology and Chronic Health Evaluation IV-predicted risk of death was also lower in SGLT2 inhibitors users. Admissions and mortality due to sepsis were lower in SGLT2 inhibitor users compared with DPP-4 inhibitor users (admissions for sepsis: 45 [0.4%] vs 134 [0.8%]; p = 0.001 and mortality: 59 [0.6%] vs 414 [2.3%]; p < 0.001, respectively). CONCLUSIONS: In patients with type 2 diabetes, SGLT2 inhibitors were independently associated with lower rates of ICU admission and all-cause mortality across various disease categories.