Prognostic impact of abnormal sodium burden in heart failure patients with preserved ejection fraction.

BACKGROUND: Sodium abnormality is common in patients with heart failure (HF) and is associated with adverse clinical outcomes. The aim of this study is to determine the impact of abnormal sodium burden on long-term mortality and hospitalization in HF with preserved ejection fraction (HFpEF). METHODS: We analysed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline and follow-up data (n = 1717). Abnormal sodium burden was defined as the proportion of days with abnormal sodium plasma levels (either <135 mmol/L or > 145 mmol/L). To determine the independent prognostic impact of abnormal sodium burden on the long-term clinical adverse outcomes (The primary outcome was any cause death, the secondary outcomes include cardiovascular disease death, HF hospitalization, any cause hospitalization and the primary endpoint of the original study), a multivariable Cox proportional hazard model and time-updated Cox regression model were performed. RESULTS: Abnormal sodium burden occurred in 717 patients (41.76%). A high abnormal sodium burden was associated with 1.47 (95% CI, 1.15-1.89) higher risk with any cause mortality, 1.51 (95% CI, 1.08-2.09) higher risk with CVD death and 1.31 (95% CI, 1.02-1.69) higher risk with HF hospitalization when compared with no burden group. When sodium level changes over time were accounted for in time-updated models, abnormal sodium level was still associated with poor clinical outcomes. Diuretic and spironolactone usage did not show a statistical interaction effect on the prognostic significance. CONCLUSIONS: In HFpEF patients, abnormal sodium burden was an independent predictor long-term any-cause mortality and HF hospitalization.

Prognostic significance of blood urea nitrogen/creatinine ratio in chronic HFpEF.

BACKGROUND: The prognostic significance of blood urea nitrogen (BUN)/creatinine ratio specifically in chronic heart failure with preserved ejection fraction (HFpEF) patients remained unclear. We aimed to evaluate the association of BUN/creatinine ratio (baseline level and visit-to-visit variation) with the risk of adverse clinical outcomes among patients with chronic HFpEF. METHODS AND RESULTS: This is a secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Of the enrolled 3445 participants in the TOPCAT trial, associations between BUN/creatinine and clinical outcomes were examined in a subset of 1521 (baseline measurements level) and 1453 (visit-to-visit variation) participants. A multivariable Cox proportional hazard model was used to assess the prognostic significance of BUN/creatinine ratio and BUN/creatinine ratio variation for the prespecified clinical outcomes. A higher BUN/creatinine ratio was associated with a higher risk of all-cause mortality (hazard ratio [HR] = 1.52, 95%CI, 1.21-1.91; p < .001) as well as cardiovascular disease mortality (HR = 1.83, 95%CI, 1.35-2.49; p < .001) in the fully adjusted model. Greater visit-to-visit variability in BUN/creatinine ratio tended to be independently associated with a higher risk of heart failure hospitalization and primary endpoint (p < .001 for both outcomes). Furthermore, those findings were consistent across participants stratified by the presence of chronic kidney disease at baseline. CONCLUSIONS: Higher BUN/creatinine ratio and greater BUN/creatinine ratio variability are independently associated with adverse outcomes in HFpEF participants in the TOPCAT trial.

The Use of Cerebral Oximetry in Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The evidence on the use of cerebral oximetry during surgery to minimize postoperative neurologic complications remains uncertain in the literature. The present authors aimed to assess the value of cerebral oximetry in the prevention of postoperative cognitive dysfunction, postoperative delirium, and postoperative stroke in adults undergoing surgery. DESIGN: A systematic review and meta-analysis. SETTING: The surgery room. PARTICIPANTS: Adult patients (ages ≥18 years) undergoing surgery. INTERVENTIONS: Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS: Databases of Ovid MEDLINE, Ovid EMBASE, and CENTRAL were systematically searched from their inception until December 2020 for randomized controlled trials comparing cerebral oximetry monitoring with either blinded or no cerebral oximetry monitoring in adults undergoing surgery. Observational studies, case reports, and case series were excluded. Seventeen studies (n = 2,120 patients) were included for quantitative meta-analysis. Patients who were randomized to cerebral oximetry monitoring had a lower incidence of postoperative cognitive dysfunction (studies = seven, n = 969, odds ratio [OR] 0.23, 95% confidence interval [CI] 0.11-0.48, p = 0.0001; evidence = very low). However, no significant differences were observed in the incidence of postoperative delirium (studies = five, n = 716, OR 0.81, 95% CI 0.53-1.25, p = 0.35; evidence = high), and postoperative stroke (studies = seven, n = 1,087, OR 0.72, 95% CI 0.30-1.69, p = 0.45; evidence = moderate). CONCLUSION: Adult patients with cerebral oximetry monitoring were associated with a significant reduction of postoperative cognitive dysfunction. However, given the low certainty of evidence and substantial heterogeneity, more randomized controlled trials using standardized assessment tools for postoperative cognitive dysfunction and interventions of correcting cerebral desaturation are warranted to improve the certainty of evidence and homogeneity.

Attenuation of Myocardial Dysfunction in Hypertensive Cardiomyopathy Using Non-R-Wave-Synchronized Cardiac Shock Wave Therapy.

Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in the CSWT group. The CSWT group exhibited significantly increased microvascular density and vascular endothelial growth factor (VEGF) expression in the myocardium. Cytokine array demonstrated that the CSWT group had significantly reduced inflammation compared with the hypertension group. Our results demonstrate that non-R-wave-triggered CSWT is safe and can attenuate LV systolic and diastolic dysfunction via enhancement of myocardial neovascularization and anti-inflammatory effect in a large animal model of hypertensive cardiomyopathy.

A randomized controlled trial of the effects of non-surgical periodontal therapy on cardiac function assessed by echocardiography in type 2 diabetic patients.

BACKGROUND: Periodontitis significantly increases the risk of diabetic complications. This clinical trial investigated the effects of periodontal therapy on cardiac function in patients with type 2 diabetes mellitus (T2DM) and periodontitis. MATERIALS AND METHODS: Fifty-eight subjects with T2DM and periodontitis were randomly allocated to Treatment Group (n = 29) receiving non-surgical periodontal therapy, and Control Group (n = 29) having only oral hygiene instructions with delayed periodontal treatment until completion of this 6-month study. The left ventricle (LV) diastolic function was assessed by echocardiography with the tissue Doppler imaging index (E/e' ratio); and LV hypertrophy was evaluated by LV mass index (LVMI). Blood samples were collected for biochemical analysis. RESULTS: The intention-to-treat analysis showed that periodontal treatment significantly reduced the E/e' ratio by 1.66 (95% CI: -2.64 to -0.68, p < .01), along with marked improvement of periodontal conditions (p < .05). LVMI was not altered at the 6-month follow-up. The serum levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) as a cardiac stress biomarker, C-reactive protein and interleukin-6 decreased numerically without reaching statistical significance. CONCLUSION: The present study provides the first evidence that non-surgical periodontal therapy may improve cardiac diastolic function in type 2 diabetic patients with periodontitis.

Periodontitis links to exacerbation of myocardial dysfunction in subjects with type 2 diabetes.

BACKGROUND AND OBJECTIVE: Subjects with diabetes and periodontitis are at high risk of cardiovascular events, while the subclinical alterations of cardiac function in this cohort remain unclear. This cross-sectional study investigated the association of periodontitis with left ventricle (LV) structural and functional abnormalities in subjects with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A total of 115 subjects with T2DM were divided into Control group (n = 32) with no or mild periodontitis, and the rest with moderate to severe chronic periodontitis (CP) were further categorized into CP-1 (n = 41) and CP-2 (n = 42) based on disease severity. Echocardiography was performed to precisely assess (a) LV hypertrophy by LV mass index (LVMi); (b) LV diastolic function by tissue Doppler imaging index E/e' ratio; and (c) LV systolic function by speckle tracking derived global longitudinal strain (GLS). RESULTS: Overall, a linear trend in LVMi, E/e', and GLS existed among the Control, CP-1, and CP-2 groups, respectively (P < 0.05). After adjustments of multiple confounders, CP-2 subjects showed significantly higher E/e' (log scale, 2.22 ± 0.05 vs 2.07 ± 0.06, P < 0.01) and GLS (-17.42 ± 0.46% vs -18.95 ± 0.54%, P < 0.05) than the Controls. Multivariate analysis revealed that sites% with probing depth ≥4 mm and sites% with clinical attachment loss ≥5 mm were independent indicators for E/e' (ß = 0.005 and ß = 0.002, P < 0.01) and GLS (ß = 0.03 and ß = 0.02, P < 0.05) , respectively. Moreover, the number of missing teeth was significantly associated with LVMi (ß = 0.01, P < 0.01). CONCLUSION: This study provides the first evidence that severe periodontitis is significantly associated with the exacerbation of LV diastolic and systolic dysfunction in subjects with T2DM.

Osteogenic circulating endothelial progenitor cells are linked to electrocardiographic conduction abnormalities in rheumatic patients.

BACKGROUND: Osteogenic circulating endothelial progenitor cells (EPC) play a pathogenic role in cardiovascular system degeneration through promulgating vasculature calcification, but its role in conduction disorders as part of the cardiovascular degenerative continuum remained unknown. AIM: To investigate the role of osteocalcin (OCN)-expressing circulating EPCs in cardiac conduction disorders in the unique clinical sample of rheumatoid arthritis (RA) susceptible to both abnormal bone metabolism and cardiac conduction disorders. METHODS: We performed flow cytometry studies in 134 consecutive asymptomatic patients with rheumatoid arthritis to derive osteogenic circulating OCN-positive (OCN+) CD34+KDR+ vs. CD34+CD133+KDR+ conventional EPC. Study endpoint was the prespecified combined endpoint of electrocardiographic conduction abnormalities. RESULTS: Total prevalence of cardiac conduction abnormality was 9% (n = 12). All patients except one had normal sinus rhythm. One patient had atrial fibrillation. No patient had advanced atrioventricular (AV) block. Prevalence of first-degree heart block (>200 ms), widened QRS duration (>120 ms) and right bundle branch block were 6.7%, 2.1%, and 2.2% respectively. Circulating osteogenic OCN+ CD34+ KDR+ EPCs were significantly higher among patients with cardiac conduction abnormalities (p = 0.039). Elevated OCN+ CD34+ KDR+ EPCs> 75th percentile was associated with higher prevalence of cardiac conduction abnormalities (58.3% vs. 20.02%, p = 0.003). Adjusted for potential confounders, elevated OCN+ CD34+ KDR+ EPCs> 75th percentile remained independently associated with increased risk of cardiac conduction abnormalities (OR = 4.4 [95%CI 1.2-16.4], p = 0.028). No significant relation was found between conventional EPCs CD34+CD133+KDR+ and conduction abnormalities (p = 0.36). CONCLUSIONS: Elevated osteogenic OCN+ CD34+ KDR+ EPCs are independently associated with the presence of electrocardiographic conduction abnormalities in patients with rheumatoid arthritis, unveiling a potential novel pathophysiological mechanism.

Haemin attenuates intermittent hypoxia-induced cardiac injury via inhibiting mitochondrial fission.

Obstructive sleep apnoea (OSA) characterized by intermittent hypoxia (IH) is closely associated with cardiovascular diseases. IH confers cardiac injury via accelerating cardiomyocyte apoptosis, whereas the underlying mechanism has remained largely enigmatic. This study aimed to explore the potential mechanisms involved in the IH-induced cardiac damage performed with the IH-exposed cell and animal models and to investigate the protective effects of haemin, a potent haeme oxygenase-1 (HO-1) activator, on the cardiac injury induced by IH. Neonatal rat cardiomyocyte (NRC) was treated with or without haemin before IH exposure. Eighteen male Sprague-Dawley (SD) rats were randomized into three groups: control group, IH group (PBS, ip) and IH + haemin group (haemin, 4 mg/kg, ip). The cardiac function was determined by echocardiography. Mitochondrial fission was evaluated by Mitotracker staining. The mitochondrial dynamics-related proteins (mitochondrial fusion protein, Mfn2; mitochondrial fission protein, Drp1) were determined by Western blot. The apoptosis of cardiomyocytes and heart sections was examined by TUNEL. IH regulated mitochondrial dynamics-related proteins (decreased Mfn2 and increased Drp1 expressions, respectively), thereby leading to mitochondrial fragmentation and cell apoptosis in cardiomyocytes in vitro and in vivo, while haemin-induced HO-1 up-regulation attenuated IH-induced mitochondrial fragmentation and cell apoptosis. Moreover, IH resulted in left ventricular hypertrophy and impaired contractile function in vivo, while haemin ameliorated IH-induced cardiac dysfunction. This study demonstrates that pharmacological activation of HO-1 pathway protects against IH-induced cardiac dysfunction and myocardial fibrosis through the inhibition of mitochondrial fission and cell apoptosis.

Clinical Benefit of Valvular Surgery in Patients with Chronic Kidney Disease.

Concomitant chronic kidney disease (CKD) is common in patients with significant valvular heart disease (VHD). This study sought to evaluate the clinical benefit of valvular surgery in patients with concomitant CKD.We evaluated 349 patients with significant VHD who were referred for surgery. Patients were divided into those with CKD stage ≥ 3 (CKD patients; n = 88) and those with CKD stage 1 or 2 (no CKD patients; n = 261). 63 patients did not receive surgery, of which 20 patients had CKD and 43 had no CKD. Mortality and change in eGFR were assessed after a median follow-up of 21 months.In the whole study population, 25% of the patients had CKD and these patients had higher mortality than those with no CKD. The annual mortality rates of patients with CKD who did and did not undergo surgery were 7.9% and 28.0%, respectively. In patients with no CKD, the annual mortality rates of those who did and did not undergo surgery were 1.8% and 2.3%, respectively. Importantly, surgery was associated with significant survival benefit in patients with CKD (log-rank test, P < 0.01), but was neutral in patients with no CKD. Multivariable analysis confirmed the survival benefit of valvular surgery in all patients, which was most significant in patients with CKD. Furthermore, eGFR was preserved in patients who underwent valvular surgery but declined significantly in those who did not.CKD is common in patients with significant VHD and, if left untreated surgically, these patients exhibit a high mortality.

Periodontal treatment modulates gene expression of endothelial progenitor cells in diabetic patients.

BACKGROUND: Periodontitis is closely linked with type 2 diabetes mellitus (T2DM) and endothelial dysfunction. This study investigated the effects of periodontal treatment on immuno-inflammatory gene expression of endothelial progenitor cells (EPCs) in diabetic patients. METHODS: Eighteen T2DM patients with moderate to severe chronic periodontitis were randomly assigned to the Treatment group with oral hygiene instruction (OHI), scaling and root debridement (n = 11), and Control group (n = 7) with OHI alone. Peripheral blood samples were taken for biochemical analysis and culture of EPCs at baseline and 6 months after the treatment. PCR array-based profiling of 84 Toll-like receptor signalling-related genes in EPCs was firstly assessed for four randomly selected patients from the Treatment group. The differentially expressed genes were then further validated by qPCR in both groups. RESULTS: All subjects in the Treatment group significantly improved their periodontal conditions. Among the 84 genes tested, IL-6 and IL-8 transcripts were significantly downregulated with over twofold change after the treatment, and this observation was further validated by qPCR in all subjects from both groups (p < .05). CONCLUSION: This preliminary study suggests that periodontal treatment may contribute to a notable reduction in immuno-inflammatory gene expression measured by IL-6 and IL-8 transcripts in EPCs.

Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular events. The aim of the study was to assess whether global longitudinal strain (GLS) provides prognostic value in these patients. METHODS: A total of 247 T2DM patients without history of cardiovascular complications and participated in the CDATS study were prospectively enrolled. Left ventricular (LV) systolic function was assessed by LV ejection fraction and speckle tracking derived LV systolic GLS. Diastolic function was assessed by E/E' ratio defined as the passive trans-mitral LV inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus. Cardiovascular event included acute coronary syndrome, cerebrovascular stroke, hospitalization for heart failure and cardiovascular death. RESULTS: A total of 18 cardiovascular events occurred during a median follow-up duration of 33 months. Both E/E' ratio [hazard ratio (HR) 1.15, P < 0.01] and GLS (HR 1.39, P < 0.01) were independently associated with cardiovascular events. Importantly, GLS provided incremental prognostic information in addition to clinical data, HbA1c and E/E' ratio (Chi square 77.46, P = 0.04). Receiver-operator characteristic curve analysis demonstrated that E/E' ratio [area under curve (AUC) 0.66, P = 0.03] and GLS (AUC 0.72, P < 0.01) were strong predictors of cardiovascular events. Kaplan-Meier analysis showed that patients with E/E' > 13.6 or GLS > -17.9 % were associated with cardiovascular events. The presence of either a high E/E' ratio or an impaired GLS provides an excellent negative predictive value of cardiovascular events in these patients. CONCLUSIONS: In T2DM patients with no history of cardiovascular disease, impaired GLS was associated with cardiovascular events and provided incremental prognostic value.

Left ventricular myocardial dysfunction and premature atherosclerosis in patients with axial spondyloarthritis.

OBJECTIVE: To evaluate left ventricular (LV) function and carotid intima-media thickness (IMT) in patients with axial SpA in relationship to underlying disease severity. METHODS: We recruited 104 patients with axial SpA and 50 controls. Detailed transthoracic echocardiography was performed and analysed with two-dimensional speckle tracking strain analysis for systolic function and tissue Doppler-derived E/E' for diastolic function assessment. Carotid IMT was measured by ultrasonography to evaluate subclinical atherosclerosis. Radiological severity of patients with axial SpA was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). RESULTS: Despite a similar LV ejection fraction [62.7% (s.d. 3.9) vs 62.8% (s.d. 3.8), P = 0.83], patients with axial SpA had impaired LV myocardial longitudinal strain (LS), circumferential strain (CS) and radial strain (RS) compared with controls [-18.1% (s.d. 2.4) vs -20.1% (s.d. 2.5), -17.2% (s.d. 2.2) vs -20.3% (s.d. 2.9) and 37.1% (s.d. 8.6) vs 43.2% (s.d. 10.9), respectively; all P < 0.01]. In addition, patients with axial SpA had a greater E/E' [7.9 (s.d. 2.5) vs 7.0 (s.d. 1.7), P < 0.01] and carotid IMT [0.78 mm (s.d. 0.19) vs 0.69 mm (s.d. 0.10), P < 0.01] than controls. After adjusting for potential confounding factors, axial SpA remained independently associated with LV myocardial strains, E/E' and carotid IMT. Importantly, multivariate linear regression analysis demonstrated that mSASSS was independently associated with LV longitudinal strain, E/E' and carotid IMT. CONCLUSION: Our study demonstrated that patients with axial SpA had impaired LV systolic and diastolic function and increased carotid IMT. Importantly, mSASSS was independently associated with LV longitudinal strain, E/E' and carotid IMT after adjusting for confounding factors. Speckle tracking echocardiography may be a useful tool for early detection of impaired LV function in patients with SpA and carotid IMT examination can provide valuable assessment of subclinical atherosclerosis in patients with SpA.

Altered myocardial response in patients with diabetic retinopathy: an exercise echocardiography study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) complicated by retinopathy is associated with altered left ventricular (LV) structure and resting myocardial dysfunction unlike T2DM without retinopathy. The myocardial response to stress has not been compared in patients with and without diabetic retinopathy. The aim of this retrospective study was to determine the relationship between retinopathy and myocardial function in patients with T2DM at rest and during exercise echocardiography. METHODS: 134 patients with T2DM and no evidence of underlying coronary artery disease were recruited. All patients underwent retinal photography to screen for diabetic retinopathy, and resting and exercise echocardiography. Resting echocardiography was analyzed by conventional echocardiographic parameters and speckle tracking derived global longitudinal strain (GLS). Exercise echocardiography parameters included diastolic function reserve index (DFRI) and stress GLS. RESULTS: The mean age of participants was 60 years and 49% were male. Diabetic retinopathy was identified in 43 patients (32%). Resting echocardiography revealed that those with diabetic retinopathy had a higher prevalence of impaired diastolic function, higher E/E' ratio (LV filling pressures) and impaired resting GLS compared with those without. Exercise echocardiography revealed that those with diabetic retinopathy also had more impaired DFRI and stress GLS. Multivariable analysis showed that the presence of diabetic retinopathy was independently associated with high resting E/E', diastolic dysfunction grade, impaired resting GLS, low DFRI and impaired stress GLS. CONCLUSIONS: In conclusion, the presence of diabetic retinopathy was independently associated with impaired resting myocardial function (diastolic and systolic function) and myocardial function during stress (evaluated by DFRI and stress GLS).

Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus.

INTRODUCTION: High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients. METHODS AND RESULTS: We compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 ± 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM. CONCLUSION: The present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up.

4,4'-{[1,2-Phenyl-enebis(methyl-ene)]bis-(-oxy)}di-benzoic acid di-methyl-formamide disolvate.

In the title solvate, C22H18O6·2C3H7NO, the complete dicarboxylic acid molecule is generated by a crystallographic twofold axis, which bisects the central benzene ring and one N,N-di-methyl-formamide solvent mol-ecule. The dihedral angle between the central and pendant benzene rings is 54.53 (5)° while that between the pendant rings is 45.44 (5)°. In the crystal, the acid molecules are linked to the solvent molecules via O-H⋯O and weak C-H⋯O hydrogen bonds. Further weak C-H⋯O inter-actions link adjacent acid mol-ecules into a three-dimensional network.

Hemoglobin to red cell distribution width ratio: A predictor of clinical outcome and diuretic response in patients with acute heart failure.

BACKGROUND: Hemoglobin to Red Cell Distribution Width Ratio (HRR) is a novel inflammatory marker in the prognostic assessment of tumors. Nevertheless, its focus on the cardiovascular field is relatively limited, particularly regarding its correlation with diuretic responses and clinical outcomes. METHODS: This is a secondary analysis of the Renal Optimization Strategies Evaluation (ROSE AHF) clinical trial. The outcomes of interest included all-cause death, rehospitalization and diuretic responses. Multivariable Cox proportional hazard regression and linear regression models were performed, respectively. Prognostic outcomes and diuretic response were further evaluated in ejection fraction (EF) subgroups (preserved EF ≥ 50% and reduced EF<50%). RESULTS: A total of 351 patients were included in the present study and further categorized according to HRR median (0.7131) value at admission: low HRR group (n = 176) and high HRR group (n = 175). High HRR were found to be independently associated with decreased risk of all-cause death (HR = 0.51; 95% CI,0.30-0.87, P = 0.013), reduced risk of developing all-caused death or rehospitalization (HR = 0.62; 95% CI,0.39-0.98, P = 0.039). Furthermore, high HRR indicated lower cumulative urine output (OR: -992.33, P = 0.004) and less weight loss (OR: 3.08, P < 0.001) within 72 h after diuresis. Subgroup analysis revealed no significant interaction effect between EF and HRR in prognostic impact or diuretic responses, and HRR was negatively correlated with plasma volume. CONCLUSION: High HRR demonstrated a lower risk of developing adverse clinical outcomes and a poorer diuretic response that might be due to less volume overload in AHF patients.

Estimated pulse wave velocity predicts mortality in patients with heart failure with preserved ejection fraction.

OBJECTIVE: Estimated pulse wave velocity (ePWV), a newly established arterial stiffness (AS) parameter, predicts the development of cardiovascular disease (CVD) and death in the general population or in patients with CVD risk factors. However, whether ePWV is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. Our study aimed to evaluate the prognostic value of ePWV on clinical outcomes in HFpEF. METHODS AND RESULTS: We analyzed HFpEF participants from the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline data (n = 1764). Cox proportional hazard model was used to explore the prognostic value of ePWV on long-term clinical outcomes (all-cause mortality, cardiovascular mortality, all-cause hospitalization, and heart failure hospitalization). Each ePWV increase by 1 m/s increased the risk for all-cause death by 16% (HR:1.16; 95% CI:1.10-1.23; P < 0.001) and CVD mortality by 13% (HR:1.13; 95% CI:1.04-1.21; P = 0.002) after adjusting for confounders. Patients were then grouped into 4 quartiles of ePWV. Our study indicated that the highest ePWV quartile (ePWV ≥ 12.806 m/s) was associated with increased risk of all-cause mortality (HR: 1.96; 95% CI: 1.43-2.69; P < 0.001) and CVD mortality (HR: 1.72; 95% CI: 1.16-2.56; P = 0.008) after adjusting for potential confounders. CONCLUSION: These results suggested ePWV is independently associated with increased all-cause mortality and CVD mortality in HFpEF patients, indicating ePWV is an appropriate predictor of prognosis in patients with HFpEF.

Mean corpuscular haemoglobin concentration and outcomes in heart failure with preserved ejection fraction.

AIMS: This study aims to evaluate the prognostic value of mean corpuscular haemoglobin concentration (MCHC) on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We analysed HFpEF participants from the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline data (n = 1747). Patients were grouped into hypochromia or non-hypochromia group according to a MCHC cut-off level of 330 g/L. Cox proportional hazard model was used to explore the prognostic value of hypochromia on the long-term clinical outcomes (the primary endpoint [composite of cardiovascular mortality, HF hospitalization and aborted cardiac arrest], any-cause and HF hospitalization, all-cause and cardiovascular mortality). Patients were further stratified according to baseline estimated glomerular filtration rate (eGFR) to explore the impact of renal dysfunction on the prognostic value of hypochromia. Baseline hypochromia was prevalent (n = 662, 37.9%) and strongly associated with worse clinical outcomes. In patients with worse renal function (eGFR < 60 mL/min per 1.73 m2 ), hypochromia was independently associated with primary endpoint (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.23-1.98; P < 0.001), any-cause hospitalization (HR, 1.43; 95% CI, 1.20-1.71, P < 0.001) and HF hospitalization (HR, 1.40; 95% CI, 1.07-1.84; P = 0.015), whereas no significant association between hypochromia and these outcomes was found in patients with better renal function. CONCLUSIONS: Among HFpEF patients, hypochromia (i.e. MCHC ≤ 330 g/L) is independently associated with adverse clinical outcomes, especially when in the presence of co-morbidity renal dysfunction.

Deformation Prediction Theory of Thermal Barrier Coatings near Cooling Holes under Thermal Cycling.

Thermal barrier coating (TBC) systems are widely adopted in gas turbine blades to improve the thermal efficiency of gas turbine engines. However, TBC failure will happen due to the thermal stress between the different layers of the TBC systems. The traditional two-layer theoretical model only considers TGO (thermally grown oxide) and a substrate in the inner cooling hole with the surface uncoated, which results in poor prediction of the deformations of the TBC systems. It should be mentioned that the effect of TBC is very important because the thickness of TBC is much larger than the TGO thickness. In this study, a new three-layer theoretical model was derived, which is composed of the cylindrical TGO and TBC mounted in the substrate with a circular hole, and the stress and strain of TGO near the cooling hole under the condition of the thermal cycles were calculated. The high temperature characteristics of TGO and the substrate including the high temperature strength and growth ratio were from the experiments. The results show that the strain of the developed three-layer model is irrelevant with increasing number of cycles, which indicates that TBC in the cooling hole significantly inhibits the deformation of TGO near the cooling hole. Therefore, aimed at confirming the feasibility of the three-layer theoretical model, the finite element analysis with coating in the cooling hole and on the surface was carried out with a three-layer axisymmetric model, which proves that the 3-layer theoretical model can predict the deformation trend near the cooling hole.

Salt restriction and risk of adverse outcomes in heart failure with preserved ejection fraction.

BACKGROUND: The optimal salt restriction in patients with heart failure (HF), especially patients with heart failure with preserved ejection fraction (HFpEF), remains controversial. OBJECTIVE: To investigate the associations of cooking salt restriction with risks of clinical outcomes in patients with HFpEF. METHODS: Cox proportional hazards model and subdistribution hazards model were used in this secondary analysis in 1713 participants with HFpEF from the Americas in the TOPCAT trial. Cooking salt score was the sum of self-reported salt added during homemade food preparation. The primary endpoint was a composite of cardiovascular death, HF hospitalisation and aborted cardiac arrest, and secondary outcomes were all-cause death, cardiovascular death and HF hospitalisation. RESULTS: Compared with patients with cooking salt score 0, patients with cooking salt score >0 had significantly lower risks of the primary endpoint (HR=0.760, 95% CI 0.638 to 0.906, p=0.002) and HF hospitalisation (HR=0.737, 95% CI 0.603 to 0.900, p=0.003), but not all-cause (HR=0.838, 95% CI 0.684 to 1.027, p=0.088) or cardiovascular death (HR=0.782, 95% CI 0.598 to 1.020, p=0.071). Sensitivity analyses using propensity score matching baseline characteristics and in patients who prepared meals mostly at home yielded similar results. Subgroup analysis suggested that the association between overstrict salt restriction and poor outcomes was more predominant in patients aged ≤70 years and of non-white race. CONCLUSION: Overstrict cooking salt intake restriction was associated with worse prognosis in patients with HFpEF, and the association seemed to be more predominant in younger and non-white patients. Clinicians should be prudent when giving salt restriction advice to patients with HFpEF.