Failure Factors Research Articles

The impact of anemia on prolonged ventilator use in critically ill patients: A literature review

Anemia is a common condition associated with critically ill patients admitted to intensive care unit (ICU), where 60% of ICU patients experience anemia and 61% of anemic and tranfused patients present in the ICU require mechanical ventilation. The presence of anemia in critically ill patients is associated with increased risk of mortality, cardiovascular morbidity, and decreased oxygen-carrying capacity, potentially prolonging the need for mechanical ventilation. Mechanical ventilation is the primary method of supporting organ function for patients receiving treatment in the ICU. According to epidemiological studies, up to 70% of patients hospitalized to the ICU require mechanical ventilation at some time during their stay. Studies regarding the correlation between anemia and the length of ventilator use are rarely known. Therefore, researchers are interested in conducting research on the correlation between anemia and length of ventilator use. This review is expected to be useful for enriching knowledge about the relationship between anemia and length of ventilator use in critically ill patients. However, further research is needed with more comprehensive variables to determine the impact of anemia on prolonged ventilator use, risk factors of weaning failure, pathogenesis of anemia, and treatment used in critically ill patients.

Prevalence of stage B heart failure in healthy adults and people with type 2 diabetes

Abstract Introduction People with Type 2 Diabetes (T2D) are at increased risk of heart failure, and as such are classified as having Stage A Heart Failure (SAHF). Those with additional evidence of raised filling pressures, biochemical or structural cardiac changes, without heart failure symptoms, are deemed to have Stage B heart failure (SBHF). Identifying patients with SBHF may help determine those at highest risk of disease progression. Purpose The aim of this work was to assess the prevalence of SBHF in a cohort of asymptomatic healthy volunteers and people with T2D characterised according to current American Heart Association/American College Cardiology/Heart Failure Society of America. Methods A single-centre, prospectively recruited cohort of middle-aged asymptomatic adults with T2D and healthy volunteers, with no history or signs of cardiovascular disease, underwent comprehensive cardiac phenotyping with transthoracic echocardiography and circulating brain natriuretic peptide. Healthy volunteers with risk factors for heart failure, including hypertension and obesity, were excluded from analysis. Prevalence of SBHF was determined by comparing cardiovascular data to proposed standards, left ventricular ejection fraction and global longitudinal strain parameters were omitted from analysis due to data availability. Results We included 383 T2Ds (diabetes duration 9(5,15) years) and 65 healthy volunteers (Table 1); 91% of those with T2D and 65% of healthy volunteers met ≥1 criteria for SBHF (Table 2). Median number of SBHF criteria met in the T2D cohort was 3 (2,4); in particular, a large proportion of the cohort met defined cut offs for relative wall thickness (70.6%), lateral e’ (62.2%), septal e’ (54.1%) and LV wall thickness (47.4%). Of the 65 healthy volunteers, median number of SBHF criteria met was 1 (0,2.5). In healthy volunteers, SBHF was most commonly defined by lateral e’ (40.0%), septal e’ (38.3%), relative wall thickness (32.2%), left atrial volume indexed (22.4%) and serum brain natriuretic peptide (23.3%). Of note, brain natriuretic peptide levels met current SBHF parameters in 18.8% of healthy volunteers and 9.9% people with T2D, which may be attributable to the exclusion of obesity in the healthy volunteer group. Conclusion Using currently proposed standards, a high proportion of middle-aged asymptomatic people with T2D, and healthy volunteers without any risk factors for heart failure, would be categorised as having SBHF. These data strongly suggest that the majority of the proposed parameters for the definition of SBHF are not specific for a UK population and if applied will incorrectly classify many asymptomatic people at high risk of developing heart failure.

Association between impaired left ventricular global longitudinal strain and B-type natriuretic peptide in obstructive hypertrophic cardiomyopathy

Abstract Background Left ventricular global longitudinal strain (LV-GLS) is considered valuable in explaining impaired left ventricular contractility in hypertrophic cardiomyopathy (HCM) with preserved ejection fraction and is associated with worse outcome. Elevated B-type natriuretic peptide (BNP) is a biomarker of increased LV wall stretch and a risk factor of heart failure, mortality, and other adverse cardiovascular events. However, relationship between GLS and BNP has not received sufficient attention in the obstructive variant of HCM. Purpose This study aimed to determine the association between echocardiographic LV-GLS and plasma BNP in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods A total of 145 consecutive patients (32% females) with symptomatic HOCM were enrolled in the retrospective study. HOCM was defined with a maximum end-diastolic wall thickness ≥15mm without other etiologies for LV hypertrophy, and peak LV outflow tract (LVOT) gradient ≥30mmHg. The echocardiographic parameters regarding LV geometry, loading conditions, and GLS were evaluated according to guidelines. Patients were divided into two groups according to absolute GLS values (greater or lower than median LV-GLS). Patient baseline clinical data, echocardiographic parameters, and BNP were compared. Univariate and multivariable regression analysis were applied to identify the independent determinator of LV-GLS. Results The median value of LV-GLS of this study cohort was -13.4%. Eighty-one patients (47.6±13.4 years-old) had a |GLS|≥13.4% and 64 individuals (48.7±12.6 years-old) had a |GLS|<13.4%. No differences were found in age, gender, physical examinations, LVEF, cardiovascular comorbidities, or active medications between the two groups, except for body mass index (BMI). Patients with |GLS|≥13.4% had statistically lower BMI (24.58±2.42 vs. 26.00±3.12kg/m², p=0.030). BNP was found significantly elevated in patients with |GLS|<13.4% when compared with individuals with |GLS|≥13.4% {median (IQR); 550.05 (214.50, 899.35) vs. 182.40 (78.90, 479.90)pg/mL, p=0.004}. In univariate regression analysis, decreased |GLS| was associated with male gender, maximum and mean LV wall thickness, peak LVOT gradient, reduced mitral annular e’ velocity, elevated BNP and cardiac troponin I. In multivariable regression analysis, GLS was found independently associated with mean LV wall thickness and BNP. Conclusions In patients with symptomatic HOCM with preserved ejection fraction, impaired LV-GLS was found to be associated with plasma BNP and mean LV wall thickness, independent of gender, age, loading conditions, LVEF, or LVOT gradient. Reduced GLS may be a more sensitive surrogate in assessing increased myocardial wall tension or stretch, rather than LV contractility in these patients. Therefore, the interpretation of GLS in HOCM should shift away from systolic interest toward emphasizing its potential value in risk stratification of diastolic heart failure with preserved LVEF.Figure 1

Trajectories of weight and their impact on cardiac remodeling and function 16 years after bariatric surgery

Abstract Introduction Obesity is a major risk factor for heart failure, particularly heart failure with preserved left ventricular (LV) ejection fraction. Surgical treatment of obesity have significant beneficial short-term effects on weight loss and on cardiac function; its long-term impact on cardiac remodeling and function remains largely unknown. Purpose We examine the long-term effect of bariatric surgery on cardiac remodeling and function in adults with preserved LV ejection fraction. Methods Forty-four individuals with severe obesity [body mass index (BMI) ≥35kg/m2] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) were included. Anthropometric measurements and echocardiography were obtained at baseline, 12 months and 16 years follow-up. Results Mean age of participants (71% female) was 44 ± 8 years and body mass index (BMI) 49.6 ± 6.1 kg/m2. Bariatric surgery led to marked weight reduction and significant improvements in obesity-related metabolic conditions/comorbidities (hypertension, dyslipidemia, type 2 diabetes). Mean percentage of weight loss at 12 months was 37.1 ± 7.0 %. Percentage of weight regain at 16 years averaged 8.9 ± 35.0 %. Bariatric surgery was associated with a significant reduction in indexed LV mass and LV hypertrophy (p <0.01), and improvement in LV diastolic function parameters (p <0.01) at 12 months. In many participants, cardiac remodeling parameters deteriorated at 16 years follow-up compared to the echocardiographic measurements taken at 12 months post-surgery. Prevalence of LV diastolic dysfunction increased at 16 years (81 vs. 38%; p<0.001), even after adjusting for age. Weight regain at 16 years (regaining >10% of weight lost; n=25; 57%) was not found to be associated with a worsening in cardiac remodeling compared to those who maintained weight loss, except for indexed LV mass (-9.3 ± 10.6 vs. -5.5 ± 7.8 g/m2.7; p=0.04) and LV end-diastolic diameter (-5.4 ± 4.0 vs. -3.5 ± 3.3 cm; p=0.01). Conclusion Bariatric surgery (BPD-DS) leads to durable long-term weight loss. Weight regain following bariatric surgery does not appear to have adverse effect on cardiac remodeling and function. Surgical treatment of obesity may be an effective and safe way to prevent clinical cardiac dysfunction and heart failure related to obesity.

Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation

Abstract Background Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic. Purpose We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF. Methods We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin < 12 g/dL in females and hemoglobin < 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status. Results A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (< -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p < 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%. Conclusions Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.

Sex-biased proteomic regulation in obesity

Abstract Background Obesity is a major risk factor for heart failure with preserved ejection fraction, particularly in women. Obesity-associated inflammation is thought to contribute to this relationship. However, the role of biological sex in the regulation of circulating inflammatory proteins in obesity is not well understood. Purpose We aimed to explore sex differences in the plasma inflammatory protein profile in obese subjects. Methods Clinical data and samples were collected from 450 women and men with a body mass index (BMI) >27 kg/m² without known cardiovascular disease participating in the FAT associated CardiOvasculaR dysfunction study. Obesity was defined as BMI≥30 kg/m². Olink’s Target 96 inflammation panel, which profiles 92 proteins using proximity extension assay technology, was analysed in biobank samples. A comprehensive correlation analysis was performed to describe relationships between protein biomarkers and clinical variables. Gene enrichment analysis was performed to shed light on biological pathways associated with differentially expressed proteins (DEPs). To determine the functional significance of the DEPs, we used the repositories Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Pearson correlation coefficients were calculated to assess linear associations between the DEPs and relevant clinical variables. Results Women and men did not differ by age (49±9 vs 48±9 years), BMI (32.3±4.6 vs 31.6±3.7 kg/m²) or in prevalences of diabetes (both 11%) or obesity (65% vs 62%) (all p>0.05). However, hypertension was more common in men than women (74% vs 52%, p<0.001). In men (n=188), obesity was associated with downregulation of monocyte chemotactic protein 3, tumor necrosis factor (ligand) superfamily member 12, interleukin 10 and protein S100-A12 and with upregulation of neurotrophin-3 (all p<0.05), thereby suggesting a mechanism for the observed impaired inflammatory response and insulin resistance. In women (n=262), obesity was associated with the downregulation of interleukin 7, interleukin 12 subunit beta, interleukin 6, and C-X-C motif chemokine 11, suggesting a state of persistent low-grade inflammation. In addition, the upregulated sulfotransferase 1A1 and SIR2-like protein 2 proteins indicate a physiologic adaptation to oxidative stress and the metabolic excess endemic to obesity. Conclusion We found that the abundance of several circulating inflammatory proteins was altered in presence of obesity, and that the plasma proteomic profile differed by sex. Interestingly, there was no overlap in the DEPs between women and men in the presence of obesity. These findings support the hypothesis that the pathophysiological mechanisms driving obesity-associated inflammation and immune dysregulation differ by sex. In turn, this may aid in the pursuit of discovering sex-specific biomarkers to identify obese individuals at particular risk of heart failure.

The prognostic impact of renal dysfunction and anemia in japanese heart failure patients stratified by left ventricular ejection fraction

Abstract Background Renal dysfunction and anemia have been reported to be important prognostic factors in heart failure (HF) patients, but the differences in their effects stratified by left ventricular ejection fraction (LVEF) are not clear. Therefore, we investigated the prognostic impact of renal dysfunction and anemia in Japanese HF patients stratified by LVEF. Methods We combined two registry studies of acute HF patients in Japan and examined major events and associated factors during 2-year observation period. The primary endpoint was defined as all-cause mortality or HF hospitalization. Renal dysfunction was defined as eGFR <60 mL/min/1.73 m2, and anemia was defined as hemoglobin <13 g/dl in men and 12 g/dl in women. Two groups were also analyzed by LVEF (LVEF >50% and LVEF <49%). Results A total of 2142 patients were enrolled and analyzed. The mean observation period was 623±244 days. Mean age was 78.7 years. Forty-nine percent were male. Coronary artery disease and atrial fibrillation were present in 31% and 44% of patients, respectively. Medications included beta-blockers in 61% of patients and RAS inhibitors in 53%. Renal dysfunction was present in 1676 patients (74%) and anemia in 1523 patients (67%). Combination of both was observed in 1190 patients (53%). The primary endpoint was observed in 1015 patients, with 563 deaths and 737 HF hospitalizations. Multivariate analysis in a Cox proportional hazards model showed that renal dysfunction alone (HR: 1.39, 95%CI:1.06-1.81, p=0.02) and combination of renal dysfunction and anemia (HR 1.72, 95%CI:1.34-2.21, p<0.01) were independent prognostic factors in all patients. In patients with LVEF <49%, renal dysfunction alone (HR: 1.50, 95%CI:1.04-2.16, p=0.03) and combination of renal dysfunction and anemia (HR: 1.90, 95%CI:1.34-2.68, p<0.01) were predictive factors. On the other hand, in patients with LVEF >50%, only the combination of renal dysfunction and anemia were independent predictors (HR: 1.46, 95%CI:1.01-2.10, p=0.04). Conclusion We identified differences in the prognostic impact of anemia and renal dysfunction by LVEF.

Prevalence and outcomes of American Heart Association stages of heart failure in an adult brazilian population of the ELSA-Brasil study

Abstract Aims Heart failure (HF) has a major impact on public health, affecting up to 2% of adult population. HF staging is helpful in capturing pre-clinical disease and its progression to advanced stages. We aimed to determine the prevalence and mortality of HF stages in the participants of a Brazilian adult cohort. Methods The ELSA-Brasil cohort comprises 15,105 adult public servants from 6 Brazilian capitals. In the initial evaluation of the study (2008-2010), ELSA carried out interviews and clinical, laboratory, and cardiovascular ancillary tests. In this analysis, we included participants who had electrocardiogram and echocardiogram performed at baseline visit, and additional information regarding risk factors and functional capacity. The HF stages were defined based on AHA guidelines criteria as follow: Stage 0 was defined as a healthy individual with no risk factors for heart failure. Stage A (at risk for HF) included those without cardiac structural or functional abnormality but with any of the following conditions: systemic hypertension; diabetes mellitus, obesity, history of myocardial revascularization, history of rheumatic fever, and seropositivity for Chagas’ disease. Stage B (pre-HF) was defined as asymptomatic participants with history of myocardial infarction or any major abnormalities on ECG or echocardiogram. Stage C (symptomatic HF) included participants with a clinical history of HF, or HF symptoms in the presence of structural heart disease (defined as in Pre-HF stage). Considering the community-dwelling profile of the sample, we did not expect to have advanced heart failure patients in our sample. Results We included the 3,267 participants (61±9 years; 53% women) with baseline data. Prevalences of HF stages were stage 0: 938 (29%) A: 1,385 (42%), B: 651 (28%) and C: 293 (9%), with different distribution between sexes (p<0.001). Older participants had higher prevalences of stages B and C (p<0.001), with the prevalence of stage C increasing from 1.8% at 35-44 years to 12.2% at 65-74 years. After 12 years of follow-up, total mortality rates of HF stages were Stage 0: 4%; A:10%. B: 16%, and C: 26%, and respective Cox proportional hazard ratios [95% CI] adjusted for age and sex were A: 1.94 [1.3-2.8], B:2.78 [1.9-4.1], and C: 5.39 [3.6-8.1] compared to stage 0. Conclusions The prevalence of HF in Brazilians reflects what is described in international literature, with a large proportion of individuals in pre-symptomatic stages. A notable shift in the sample toward pre-symptomatic and symptomatic HF occurred gradually and persistently across the age span studied. Mortality rates increase incrementally across the HF stages. This information is important for understanding and planning health policies for this syndrome.

Is the female sex a risk factor for heart failure after myocardial infarction?

Abstract Background In previous observations, female sex was associated with heart failure after myocardial infarction (MI). However, women were older and had more risk factors and were not treated the same as men. Purpose Our aim was to investigate the differential impact of sex on heart failure (including cardiogenic shock) and outcome in a propensity score matched population with MI who had undergone percutaneous coronary intervention (PCI) and the association between sex, heart failure and long-term mortality. Methods Data from 3624 (30.6% women) MI patients who underwent PCI at our institution were analyzed. Propensity-score matching analysis was performed to adjust for differences in baseline characteristics between men and women. After propensity matching, the sample comprised 2170 patients (1085 women and 1085 men). Heart failure was defined by clinical criteria (bilateral pulmonary rales, S3 gallop, edema or cardiogenic shock) and/or pulmonary edema on chest X-ray and/or ejection fraction <30%. The data were analyzed using descriptive statistics. The median follow-up time was 27 months (25th, 75th percentile: 9,48). Results In hospital, 329 (16.4%) patients developed heart failure, with a similar incidence in men and women (156(15.5%) vs. 173(17.2%);p=0.33) (Figure 1). Furthermore, female sex was not associated with heart failure either univariately (OR 1.13;95%CI 0.89-1.43;p=0.31) or after adjustment for confounding factors (aOR 1.27;95% CI 0.96-1.66;p=0.093). Age, hypertension, hyperlipidemia, ST- elevation MI, and P2Y12 receptor inhibitors were associated with heart failure. We followed the patients for up to six years. At the end of the observation period, 330(16.4%) patients had died. The mortality rate was similar in both sexes (159(15.8%) men died compared to 171(17.0%) women; p=0.51) (Figure 2). In addition, sex was not associated with long-term mortality (aHR 1.11;95%CI 0.88-1.40;p=0.38) after adjusting for confounders. In-hospital heart failure was independently associated with long-term mortality (aHR 2.64;95%CI 2.04-3.41;p<0.0001). Hyperlipidemia, age, ST- elevation MI, radial access, P2Y12 receptor inhibitor and GFR were also associated with long-term mortality. Conclusions Our results suggest that sex itself is not associated with heart failure after MI when women are treated similarly to men, have similar risk factors, and are of similar age. It is more likely that women are more frequently affected by heart failure because they are older, have more risk factors, are less likely to be revascularized, and are less likely than men to be treated with guideline-recommended therapy,Heart failure in men and womenLong-term all-cause mortality

The protective role of Baz2b ablation in aging-related heart failure

Abstract Background The elderly population is increasing year by year. Aging has become an important risk factor for cardiac dysfunction and heart failure. Previous studies have found that bromodomain adjacent to zinc finger 2B (Baz2b) is closely associated with neurodegeneration, but its role in aging-related heart failure remains unclear. Purpose We aim to explore the mechanism of Baz2b in aging-induced heart failure and doxorubicin-induced heart failure. We also investigate whether Baz2b and its downstream mechanism can serve as targets for clinical intervention. Methods We injected doxorubicin intraperitoneally in Baz2b knockout and cardiac-specific Baz2b knockdown mice to produce in vivo models. The effects of Baz2b and its downstream regulators were further explored via RNA-sequence, chromatin immunoprecipitation-sequence (ChIP-seq) and assay for transposase-accessible chromatin-sequence (ATAC-seq). Besides, we elucidated the function of Baz2b in alpha-myosin heavy chain-induced myocarditis. Results we found that Baz2b expression was upregulated in both aged and doxorubicin-induced mice heart. Baz2b knockout resulted in cardiac function recovery accompanied by a decline in apoptosis in aged mice and doxorubicin-induced mice. In contrast to control mice, cardiac-specific Baz2b knockdown alleviated doxorubicin-induced cardiac dysfunction and apoptosis. Mechanistically, Baz2b was closely associated with inflammatory responses in heart. It regulates Stat1, an important inflammatory downstream regulator via H3k4me3. Furthermore, the overexpression of Stat1 was able to abolish the protective role of Baz2b in doxorubicin-induced cardiotoxicity. Besides, cardiac-specific Baz2b knockdown could alleviated myocarditis, in line with the fact that Baz2b was linked to inflammation. Conclusion Taken together, this study provides new insights that Baz2b plays an important role in aging-related heart dysfunction. Since epigenetic readers were previously unrecognized, these findings may shed on novel clinical therapeutic choice for patients with chemotherapy-induced cardiotoxicity.The schematic diagram of Baz2b in heart

Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical diabetic cardiomyopathy

Abstract Background Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with so-called diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Purpose This study aimed to evaluate associations between NT-proBNP concentrations, clinical characteristics, echocardiographic findings, health status and activity, and outcomes from cardiopulmonary exercise testing Methods The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial (ARISE-HF) trial is evaluating the effects of AT-001, a novel aldose-reductase inhibitor in participants with DbCM without a prior history of heart failure (1). Participants were included if they had a known diagnosis of type 2 diabetes and age ≥60 (or ≥45 with a duration of diabetes of ≥10 years or estimated glomerular filtration rate ≤60 mL/min/1.73m2). Participants were required to have evidence of one of: structural cardiac abnormality, elevated cardiac biomarkers, or impaired exercise tolerance, defined as a peak oxygen uptake (VO2) ≤75% of predicted. In this prespecified subgroup analysis of the ARISE-HF trial, 685 participants with baseline echocardiography data, laboratory investigations, and functional assessment were included. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results The mean age of participants was 67.4 years and 50% were female. The mean duration of type 2 diabetes was 14.5 years with a mean hemoglobin A1c of 6.98. The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/e’, or right ventricular systolic pressure (Figure 1). In contrast, NT-proBNP was significantly correlated with components of the Kansas City Cardiomyopathy Questionnaire (P<0.001), the Physical Activity Scale in the Elderly (P=0.004), duration of cardiopulmonary exercise testing (P<0.001), peak VO 2 (P<0.001), and ratio of minute ventilation/carbon dioxide production (P=0.002; Figure 2). Conclusion Among highly selected patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals.

Clinical impact of serum cholinesterase level on clinical outcomes in patients with lower extremity artery disease undergoing endovascular treatment

Abstract Background Cholinesterase (ChE) has been used to be an indicator of the protein synthesis ability in the liver and nutritional status. Recent findings have identified low ChE levels as a prognostic factor for heart failure. However, the relationship between serum ChE levels and clinical outcomes in patients with lower extremity artery disease (LEAD) undergoing endovascular treatment (EVT) remains unclear. Purpose This study aimed to investigate the association between pre-procedure serum ChE levels and clinical outcomes in LEAD patients undergoing EVT. Methods The subjects were 283 consecutive LEAD patients who underwent EVT at our University Hospital were included. The primary outcome measure was the cumulative incidence of major adverse cardiovascular events (MACEs) within two years, defined as the composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke. Results The mean age of the cohort was 72.6±10.6 years, with 67.5% being male. Within two years, 45 patients experienced MACE, and Kaplan-Meier curves demonstrated the cumulative incidence of MACE within two years was 19.3%. Receiver operating characteristic curve analysis showed that serum ChE was a univariable factor that predicted MACE within two years with moderate accuracy (area under the curve = 0.693, 95% confidence interval (CI) 0.615–0.771), with an optimal serum ChE cutoff level of 284 units/L. According to the optimal cut-off value, patients were divided into low ChE (ChE ≤ 284 units/L, N=189) and high ChE ((ChE > 284 units/L, N=94) groups. In the baseline characteristics between the two groups, age was significantly higher in the low ChE groups than in the high ChE group. There were no significant differences in gender, the prevalence of diabetes mellitus, hypertension, and the proportions of previous stroke, and previous myocardial infarction between the two groups. In contrast, the proportions of hemodialysis (HD) and chronic limb-threatening ischemia (CLTI) were higher in the low ChE groups. Kaplan-Meier curves demonstrated a significantly higher cumulative incidence of MACE in the low ChE group compared to the high ChE group (log-rank p < 0.001). In multivariate analysis using Cox proportional hazards models adjusting for risk factors, including HD and CLTI, low ChE group was independently associated with MACE (low ChE group: hazard ratio (HR) 4.24, 95% confidence interval (CI) 1.24-14.49, p=0.021). In addition, Cox proportional hazards models using serum ChE level and HD revealed that patients with both low-ChE and HD showed a greater risk of MACE (HR 15.19; 95% CI 3.60–64.02; P < 0.001) after EVT as compared to patients with neither low-CHE nor HD. Conclusions In LEAD patients undergoing EVT, lower ChE levels were independently associated with a higher risk of MACE, regardless of HD. Assessment of serum ChE level may provide insights into identifying high-risk LEAD patients who need careful attention after EVT.

Estimation of salt intake from urinalysis as a prognostic indicator in patients with heart failure

Abstract Background Restricting sodium consumption by reducing salt intake is crucial in heart failure management. The average salt intake in Japan is approximately 10 g/day, which is significantly higher than that in other countries. Therefore, the Japanese guidelines for heart failure recommend a target salt intake of less than 6 g/day. Purpose Excessive salt intake is a well-known risk factor for heart failure, but it has also been reported that excessive salt restriction does not affect clinical outcomes in patients with heart failure. Moreover, although previous reports have mainly focused on clinically stable patients with chronic heart failure, appropriate salt intake management in patients with unstable heart failure immediately after hospital discharge remains unexplored. Therefore, this study aimed to investigate the effect of salt intake management on patients with heart failure in the early post-discharge period. Methods The study was conducted between April 2015 and March 2023, and included 395 of 4,292 patients (mean age: 72 y; sex: 63% male) who were hospitalized owing to heart failure and whose salt intake was measured at early post-discharge. Salt intake was estimated via the Tanaka Method, using spot urine samples. The patients were divided into four groups based on the estimated salt intake: very low (< 4 g/day) (n = 24), low (≥ 4 and < 7 g/day) (n = 109), high (≥ 7 and < 10 g/day) (n = 149), and very high (≥ 10 g/day) (n = 113). The primary endpoint was all-cause rehospitalization within 1 year of discharge. Results During a median follow-up period of 303 days, 153 rehospitalization occurred. 96 were heart failure rehospitalization; others included infection, arrhythmia, dehydration etc. Spline curve analysis for estimated salt intake and rehospitalization (Fig. 1) showed a significant nonlinear curve (P = 0.017). Cox regression analysis (Fig. 2) revealed a significantly higher number of rehospitalization in the very low group (hazard ratio [HR]: 2.29; 95% confidence interval [CI]: 1.24–4.25; P = 0.009), compared with the low group, and a similar trend was also observed in the very high group (HR: 1.51; 95% CI: 0.99–2.31; P = 0.056). Subgroup analysis (Fig. 3) showed that the impact of estimated salt intake on rehospitalization, as represented by a U-shaped curve, was more pronounced in patients who were not treated with loop or thiazide diuretics. Conclusion The results of this study suggest that both excessive salt intake and excessive restriction may increase the risk of rehospitalization in patients with heart failure during the early post-discharge period. Additionally, the results indicate that estimation of salt intake using the Tanaka method may be particularly useful for patients not undergoing diuretic treatment. Conversely, patients with very low salt intake, potentially indicative of inadequate oral intake due to an impaired general condition, may require careful follow-up.

Managing a 4000-participant cohort with a novel mobile app: data from the RisCoin study in Germany

Abstract Issue RisCoin, a prospective monocentric longitudinal observational study, aimed to identify risk factors for COVID-19 vaccine failure. Secondary aim is to monitor symptoms, SARS-CoV-2 infection, vaccination status of 3816 enrolled healthcare workers (HCW) and 180 patients with inflammatory bowel disease (IBD). Since the LMU University Hospital Munich served both as study sponsor and employer of the HCW, a secured approach was required. Description of the solution Participants accessed the study app (CentraXX, KAIROS GmbH, Germany) via pseudonymized Contact-ID with irreversible anonymization after 6 months. Key app features were the serological results report, bidirectional messaging, and weekly survey for self-reported data on vaccinations, infections, and symptoms. Active app use was defined as submitting >1 weekly survey during the study period 10.2021-12.2022. Results Over 15 months, our study team maintained 1964 two-way communications with 958 participants via the app. Of 3979 participants with app access, 3622 (91%) were active users, 2606 (65%) submitted 1 to 11 surveys, 1016 (26%) made ≥12 submissions (P75, “frequent users”). Frequent users were more likely to be IBD patients (p = 0.001), female (p < 0.001), aged 60 or older (p < 0.001). Staff in administration and nurses were more likely to be frequent users compared to physicians (p < 0.001). Main problems included the initial operational system disparities resulting in app crashes and continuous need for app reactivation. Both led to loss of active participants and required substantial staff resources to onboard and support participants during the study. Lessons The study app enabled secure, flexible, bidirectional communication with all participants. Despite technical issues, the majority actively used the app and provided valuable longitudinal data through weekly survey submissions. Key messages • A study-specific app provides a flexible and secure bidirectional anonymous communication for the study team and participants. • Adherence to app-based communication and data collection for pandemic monitoring was particularly high among patients, nurses and administrative staff.

Obesity paradox exists in super elderly patients with heart failure

Abstract Background Aging and obesity are two global concerns in public health. As obesity is associated with several metabolic disorders, it is a well-known risk factor of heart failure (HF). However, several studies have suggested that obesity may have paradoxical survival benefits in patients with HF. Therefore, the aim of this study was to investigate whether the obesity paradox exists in super elderly patients with HF in Japan. Methods A total of 4,292 patients from our hospital HF registry were divided into four age subgroups: (A) less than 65, (B) elderly 65-74, (C) high elderly 75-84, (D) super elderly ≥85. The primary endpoint was the all-cause death within 1-year after discharge. Results At baseline, the proportion of men in each group was 42-76%, the mean left ventricular ejection fraction was 49-61%, the average of N-terminal pro-B-type natriuretic peptide was 1972-2944 pg/ml, and the mean body mass index (BMI) ranged 21-25 kg/m2. Patients with higher BMI were more common in the younger age group, while those with lower BMI were more common in the older age group. Cubic spline curves of Cox proportional hazard regression models demonstrated an inverse relationship between BMI and mortality (Fig. 1). Lower BMI was associated with higher all-cause mortality in all ages, although this association was attenuated at the young age, and pre-obesity (25–29.9 kg/m2) was associated with the greatest survival benefit. Meanwhile, the impact of underweight (<18.5 kg/m2) was stronger super elderly subjects, a one-unit increase in BMI was associated with a 10.3% decrease in the hazard ratio of death (P=0.021). Kaplan-Meier curves for all-cause mortality also showed that lower BMI was associated with higher all-cause mortality in all groups, and the differences were statistically significant in Groups B, C, and D (Fig. 2). Conclusion Our study suggested the existence of the obesity paradox among HF patients in super elderly. Mildly overweight may be beneficial at old age with HF.

International case studies: success and failure factors for digital transformation in healthcare

Abstract Background The digitalization of healthcare systems is expected to lead to improvements in the quality and efficiency of healthcare services. Despite Germany’s leading economic and technological position, the implementation and utilization of digital health solutions is lagging far behind internationally. A look at other countries shows that the digital transformation in healthcare can be successful, and that financial resources and available technologies are not the only determining factors. Rather, it is a matter of political processes, the interests of different stakeholders and the acceptance of patients and HCPs. Methods While the impression often arises that the selection of countries in case studies is random, eight international case studies were identified using a scientific method. A systematic and multi-stage process was developed to select the case studies, taking into account various relevant criteria (e.g. degree of digitalization, geography, economy). The implementation and use of various digital health tools will be examined in selected countries and healthcare systems, in which the digitalization of the healthcare system is particularly advanced. Semi-structured interviews will be conducted with experts from the international healthcare systems between fall 2024 and summer 2025. The findings will inform the development of recommendations for actions for policymakers in Germany. Conclusions This study aims to provide new insights into the key success and failure factors for the digital transformation of healthcare systems. Recommendations for action, tailored specifically to the German healthcare system and aimed at policymakers, are intended to support decision-makers in setting the course for a successful further transformation towards digital health. Key messages • International case studies will be used to identify factors that contribute to the success or failure of digital transformation in healthcare systems. • Based on the findings of this research, recommendations for action will be developed for policymakers in Germany to set the course for the successful further digitalization of healthcare.

Probabilistic Modeling Geometric Tolerance and Low Cycle Fatigue Life of Gas Turbine Compressor Blade

Abstract This paper presents a probabilistic low cycle fatigue (LCF) assessment for geometric tolerances on high load contact surfaces of gas turbine compressor blades. The typical patterns of the geometric deviations for the root contact flank of the compressor blades are identified and characterized according to coordinate measurement machine (CMM) measurements of the blade root. These typical patterns are closely related to the root form manufacture tools and process. Finite element (FE) models for the typical geometric deviation patterns are created based on nodal coordinates transformation of the surface nodes on the blade root contact flanks and radius. An optimized blade root profile tolerance is established, which enables significant cost saving. The elastic-plastic FE analysis with nonlinear contact model, material strain-life test, response surface, and constrained Monte Carlo simulation are used to create a probabilistic LCF life model for the optimized tolerance. The model quantifies the effect of the geometric deviations, blade mass, and material property on the blade LCF life. The result shows that with the optimized tolerance, the probability of blade LCF failure is very low and acceptable. It is also shown that the strain life material property is the most critical factor for the LCF failure. The root profile tolerance and blade mass are seen to have a much weaker effect on the blade LCF life.

Factors associated with the effectiveness of high-flow therapy in patients with acute hypoxemic respiratory failure: An observational study

BackwardThe COVID-19 pandemic has severely tested global health systems. Non-invasive respiratory support, especially combining high-flow nasal cannula (HFNC) and continuous positive airway pressure, has effectively treated COVID-19 induced Acute Hypoxemic Respiratory Failure and reduced mortality. However, HFNC alone is more comfortable, better tolerated, and less costly than non-invasive ventilation. Understanding which patients benefit from HFNC monotherapy versus combined therapies is essential. MethodsThis observational study included patients admitted to the intermediate respiratory care unit of a COVID-19 hospital between December 2020 and September 2021. All patients treated with HFNC were included (n = 1301). HFNC failure was defined as the need for escalated therapy (non-invasive ventilation, intubation) or death. Epidemiological, clinical, non-invasive respiratory support parameters, and laboratory data were collected, and a multivariable analysis identified key determinants. ResultsHFNC was successful in 39.9 % of patients. (n = 511) Risk factors for HFNC failure included increased age, male gender, obesity, obstructive sleep apnea, higher respiratory rate, initial SpO2/FiO2 ≤ 148, and initial PaO2/FiO2 ≤ 100. An increase in the ROX Index at 24 h and slower disease progression were associated with successful treatment. These findings led to the developmet of an index to identify patients who benefit most from HFNC monotherapy. ConclusionsHFNC monotherapy can be effective for a specific profile of patients with Acute Hypoxemic Respiratory Failure due to COVID-19. This tool may help manage these patients more appropriately. Further studies are needed to determine if these findings can be applied to Acute Hypoxemic Respiratory Failure caused by other pathologies. Implications for Clinical PracticeThis study underscores the importance of early identification and management of patients at risk of HFNC failure in intermediate respiratory care units. By recognizing factors such as age, comorbidities, and respiratory indices, healthcare providers can implement targeted strategies to enhance HFNC success. These strategies may include more stringent monitoring, tailored respiratory support, and timely escalation to more intensive therapies if needed. Our findings highlight the need for a comprehensive approach to managing severe respiratory failure in critical care settings, ultimately improving patient outcomes and reducing the burden on healthcare systems.

Deubiquitinase USP47 ameliorates cardiac hypertrophy through reducing protein O-GlcNAcylation.

Cardiac hypertrophy is a crucial risk factor for heart failure when the heart is confronted with physiological or pathological stimuli. The ubiquitin-proteasome system (UPS) plays a critical role in the pathogenesis of cardiac hypertrophy. However, as a key component of the UPS, the role of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is not well understood. Here, we observed that the expression level of deubiquitinase USP47 was increased in hypertrophic hearts and angiotensin II (Ang II)-stimulated neonatal rat cardiomyocytes (NRCMs). Adenovirus-mediated gain- and loss-of-function approaches indicated that USP47 overexpression significantly attenuated Ang II-induced cardiac hypertrophy in vitro and in vivo, whereas endogenous USP47 deficiency promoted the pro-hypertrophic effect of Ang II. Further investigation demonstrated that USP47 inhibited O-GlcNAcylation in cardiomyocytes by controlling the expression of O-GlcNAcase (OGA). Mechanistically, USP47 bound, deubiquitinated, and stabilized protein arginine methyltransferase 5 (PRMT5), thus upregulating OGA expression. We found that the restoration of PRMT5 abolished the pro-hypertrophic effects of USP47 silence in vitro. Therefore, our results provide the first evidence of the involvement of USP47 in cardiac hypertrophy and identify USP47 as a potential target for hypertrophic therapy.

Multi-modal characterisation of early-stage, subclinical cardiac deterioration in patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a major risk factor for heart failure with preserved ejection fraction and cardiac arrhythmias. Precursors of these complications, such as diabetic cardiomyopathy, remain incompletely understood and underdiagnosed. Detection of early signs of cardiac deterioration in T2DM patients is critical for prevention. Our goal is to quantify T2DM-driven abnormalities in ECG and cardiac imaging biomarkers leading to cardiovascular disease. We quantified ECG and cardiac magnetic resonance imaging biomarkers in two matched cohorts of 1781 UK Biobank participants, with and without T2DM, and no diagnosed cardiovascular disease at the time of assessment. We performed a pair-matched cross-sectional study to compare cardiac biomarkers in both cohorts, and examined the association between T2DM and these biomarkers. We built multivariate multiple linear regression models sequentially adjusted for socio-demographic, lifestyle, and clinical covariates. Participants with T2DM had a higher resting heart rate (66 vs. 61 beats per minute, p < 0.001), longer QTc interval (424 vs. 420ms, p < 0.001), reduced T wave amplitude (0.33 vs. 0.37mV, p < 0.001), lower stroke volume (72 vs. 78ml, p < 0.001) and thicker left ventricular wall (6.1 vs. 5.9mm, p < 0.001) despite a decreased Sokolow-Lyon index (19.1 vs. 20.2mm, p < 0.001). T2DM was independently associated with higher heart rate (beta = 3.11, 95% CI = [2.11,4.10], p < 0.001), lower stroke volume (beta = -4.11, 95% CI = [-6.03, -2.19], p < 0.001) and higher left ventricular wall thickness (beta = 0.133, 95% CI = [0.081,0.186], p < 0.001). Trends were consistent in subgroups of different sex, age and body mass index. Fewer significant differences were observed in participants of non-white ethnic background. QRS duration and Sokolow-Lyon index showed a positive association with the development of cardiovascular disease in cohorts with and without T2DM, respectively. A higher left ventricular mass and wall thickness were associated with cardiovascular outcomes in both groups. T2DM prior to cardiovascular disease was linked with a higher heart rate, QTc prolongation, T wave amplitude reduction, as well as lower stroke volume and increased left ventricular wall thickness. Increased QRS duration and left ventricular wall thickness and mass were most strongly associated with future cardiovascular disease. Although subclinical, these changes may indicate the presence of autonomic dysfunction and diabetic cardiomyopathy.