Adverse Prognosis Research Articles

Research progress on S-palmitoylation modification mediated by the ZDHHC family in glioblastoma

S-Palmitoylation has been widely noticed and studied in a variety of diseases. Increasing evidence suggests that S-palmitoylation modification also plays a key role in Glioblastoma (GBM). The zDHHC family, as an important member of S-palmitoyltransferases, has received extensive attention for its function and mechanism in GBM which is one of the most common primary malignant tumors of the brain and has an adverse prognosis. This review focuses on the zDHHC family, essential S-palmitoyltransferases, and their involvement in GBM. By summarizing recent studies on zDHHC molecules in GBM, we highlight their significance in regulating critical processes such as cell proliferation, invasion, and apoptosis. Specifically, members of zDHHC3, zDHHC4, zDHHC5 and others affect key processes such as signal transduction and phenotypic transformation in GBM cells through different pathways, which in turn influence tumorigenesis and progression. This review systematically outlines the mechanism of zDHHC family-mediated S-palmitoylation modification in GBM, emphasizes its importance in the development of this disease, and provides potential targets and strategies for the treatment of GBM. It also offers theoretical foundations and insights for future research and clinical applications.

Significance of serum lncRNA XIST in chronic obstructive pulmonary disease and its progression to pulmonary heart disease

BackgroundChronic obstructive pulmonary disease (COPD) has become one of the major death-related causes. Chronic pulmonary heart disease (CPHD) is an adverse complication of COPD causing poor prognosis of patients. This study evaluated the role of lncRNA XIST in COPD and CPHD aiming to identify a potential biomarker for the screening and prediction of COPD.MethodsThe study enrolled 127 COPD patients, including 73 patients occurred CPHD with 76 healthy individuals as the control group. The expression of XIST was evaluated by PCR and compared between COPD patients with different severity, grades, and complications. The diagnostic and prognostic values of XIST in COPD and CPHD were assessed by ROC and Kaplan-Meier analyses.ResultsSignificant upregulation of XIST was observed in the serum of COPD patients relative to healthy individuals, which distinguished COPD patients and showed a correlation with the respiratory and pulmonary function of COPD patients. COPD patients with acute exacerbations and CPHD showed a higher expression level. Increasing serum XIST discriminated COPD patients combined CPHD and positively correlated with right ventricular hypertrophy and pulmonary hypertension. Higher serum XIST levels could indicate the adverse 3-year prognosis of COPD patients, especially for COPD patients combined with CPHD.ConclusionUpregulated XIST served as a biomarker for screening COPD and predicting adverse prognosis of COPD and COPD patients with CPHD.

Multimodal MRI changes associated with non-motor symptoms of rapid eye movement sleep behaviour disorder in Parkinson's disease patients.

Parkinson's disease (PD), a prevalent neurodegenerative disorder, assumes a more adverse prognosis when accompanied by rapid eye movement sleep disorder (RBD). Non-motor symptoms, particularly sleep and emotional disturbances, significantly impair patients' quality of life. This study aimed to investigate the neuroimaging underpinnings of PD-RBD using structural and functional magnetic resonance imaging (MRI) and to explore the associations between these imaging biomarkers and non-motor symptoms. Brain scans were acquired from 33 PD patients without and 21 with probable RBD (PD-pRBD). Comparative analyses were performed to evaluate structural and functional alterations between the two groups. Additionally, the correlations between neuroimaging metrics and clinical assessment scales were assessed. PD-pRBD patients demonstrated more pronounced grey matter atrophy, particularly in the putamen and insula. Functional MRI revealed decreased amplitude of low-frequency fluctuations (ALFF) in the bilateral posterior cingulate cortex and left precuneus of PD-pRBD patients. Furthermore, reduced functional connectivity (FC) was observed in specific regions of the whole brain and within the default mode network (DMN) in PD-pRBD. Notably, a negative correlation was found between mean ALFF values in the left posterior cingulate cortex of PD-pRBD patients and Hamilton Depression Rating Scale scores. PD-pRBD is characterized by more severe grey matter loss and functional MRI abnormalities compared to PD alone. Dysfunction of the posterior cingulate cortex is implicated in more pronounced affective impairments, providing novel insights into the complex pathophysiology of PD-RBD.

Low transthyretin concentration linked to adverse prognosis in elderly inpatients

BackgroundTo investigate the association between low transthyretin (prealbumin) concentration and mortality or readmission for all causes in elderly inpatients.MethodsThis analysis is based on a prospective cohort study conducted from September 2018 to April 2019 in ten wards of three tertiary referral hospitals in Beijing. Patients aged 65 years or older were enrolled, and their clinical data, laboratory test results, and auxiliary test results for patients were collected. A three-year follow-up was conducted with patients. Based on the 5th and 95th percentiles of transthyretin concentration, patients were split into three groups. The correlation between transthyretin concentration and the outcome of elderly hospitalized patients was investigated. The primary outcome of the research was death or readmission from all causes within three years.ResultsAmong the 636 individuals in the study, 335 (52.7%) were males, with a median age of 74.7 years (interquartile range [IQR]: 69.3–80.1). During a median follow-up period of 1,099.0 days (IQR: 1,016.3-1,135.0), 363 individuals (57.0%) experienced all-cause mortality or readmission events. Patients with transthyretin concentrations at or below the 5th percentile had a significantly increased risk of all-cause mortality or readmission compared to those with concentrations between the 5th and 95th percentiles (hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.55–3.26). Even after adjusting for potential confounders, low transthyretin concentration remained an independent risk factor for poor prognosis in elderly inpatients (HR: 1.84; 95% CI: 1.03–3.28). Since women have consistently lower baseline transthyretin levels than men, we performed gender-specific analysis. We found that low transthyretin concentration is an independent risk factor for adverse prognosis in elderly male inpatients (HR: 2.99; 95% CI: 1.35–6.62) but not in females.ConclusionsLow transthyretin concentrations are associated with increased all-cause mortality or readmission in elderly inpatients, particularly among male patients.Graphical

Application of preoperative NLR-based prognostic model in predicting prognosis of intrahepatic cholangiocarcinoma following radical surgery

PurposeTo investigate the application value of the neutrophil to lymphocyte count ratio (NLR) in the prognostic analysis of intrahepatic cholangiocarcinoma (ICC) after radical resection, and to offer guidance for the individualized perioperative diagnosis and treatment of ICC.MethodsThe clinical data of 360 patients diagnosed with ICC following radical surgery were retrospectively analyzed. The cut-off value of NLR was calculated using the minimum p-value method, and then divided into High-NLR (H-NLR) group and Low-NLR (L-NLR) group according to the NLR cut-off value. The prognostic value of NLR in ICC was analyzed. Subsequently, the patients were divided into the hepatolithiasis-related intrahepatic cholangiocarcinoma (HICC) group and the non-hepatolithiasis-related intrahepatic cholangiocarcinoma (NHICC) group based on whether they combined with hepatolithiasis. Multiple regression models were constructed based on NLR and clinicopathological indicators to verify the application value of prognostic models in the survival and recurrence of ICC patients after radical surgery.ResultsThe cut-off value of NLR was 2.36, and the survival analysis disclosed that overall ICC patients with NLR ≥ 2.36 manifested a poor 5-year survival rate and a higher tumor recurrence rate (p < 0.001). In the HICC group, patients with H-NLR presented a poor 5-year survival rate and a higher tumor recurrence rate compared with L-NLR (p < 0.001). The NLR-based survival/recurrence prediction models in the HICC group demonstrated excellent predictive capacity (H-L test: 0.359/0.680, AUC: 0.764/0.791). In the NHICC group, patients with H-NLR exhibited a poor 5-year survival rate compared with L-NLR (p < 0.001), yet there was no significant difference in tumor recurrence between the two groups (p = 0.071). The NLR-based survival prediction model in the NHICC group demonstrated acceptable predictive ability (H-L test: 0.268, AUC: 0.729), while the NLR-based recurrence prediction model did not show an effective predictive ability (H-L test: 0.01, AUC: 0.649).ConclusionNLR is an independent risk factor influencing postoperative survival and recurrence in ICC patients, particularly in HICC patients. Preoperative NLR ≥ 2.36 suggests that patients might have a poor prognosis. The survival and recurrence prediction model constructed based on NLR and other clinical indicators demonstrates good prediction accuracy and can effectively predict the risk of postoperative adverse prognosis in patients with HICC. This study offers a novel idea for the clinical treatment of HICC patients.

METTL3 confers oxaliplatin resistance through the activation of G6PD-enhanced pentose phosphate pathway in hepatocellular carcinoma.

Oxaliplatin-based therapeutics is a widely used treatment approach for hepatocellular carcinoma (HCC) patients; however, drug resistance poses a significant clinical challenge. Epigenetic modifications have been implicated in the development of drug resistance. In our study, employing siRNA library screening, we identified that silencing the m6A writer METTL3 significantly enhanced the sensitivity to oxaliplatin in both in vivo and in vitro HCC models. Further investigations through combined RNA-seq and non-targeted metabolomics analysis revealed that silencing METTL3 impeded the pentose phosphate pathway (PPP), leading to a reduction in NADPH and nucleotide precursors. This disruption induced DNA damage, decreased DNA synthesis, and ultimately resulted in cell cycle arrest. Mechanistically, METTL3 was found to modify E3 ligase TRIM21 near the 3'UTR with N6-methyladenosine, leading to reduced RNA stability upon recognition by YTHDF2. TRIM21, in turn, facilitated the degradation of the rate-limiting enzyme of PPP, G6PD, through the ubiquitination-proteasome pathway. Importantly, high expression of METTL3 was significantly associated with adverse prognosis and oxaliplatin resistance in HCC patients. Notably, treatment with the specific METTL3 inhibitor, STM2457, significantly improved the efficacy of oxaliplatin. These findings underscore the critical role of the METTL3/TRIM21/G6PD axis in driving oxaliplatin resistance and present a promising strategy to overcome chemoresistance in HCC.

Prior fecal immunochemical test positivity is associated with adverse prognosis in patients with acute ST-segment elevation myocardial infarction

Abstract Backgrounds While fecal immunochemical testing (FIT) is commonly used for disease screening, its significance in other conditions, particularly in patients with ST-segment elevation myocardial infarction (STEMI), is not extensively researched. Purpose This study aimed to investigate the impact of prior positive FIT results on the clinical prognosis of patients with STEMI. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients discharged from 72 hospitals from 2010 to 2023. A total of 76,157 patients with acute STEMI patients were enrolled. Positive FIT was defined as "+-" or higher on the fecal occult blood test. Propensity score matching (PSM) was employed to balance differences between the two groups. Kaplan-Meier analysis with log-rank tests compared endpoint risks between groups, and a multivariable Cox regression model adjusted for potential confounders. The primary endpoint was Net Adverse Clinical Event (NACE), including cardiac death, recurrent myocardial infarction, revascularization, stroke, cerebral hemorrhage, and gastrointestinal bleeding. Results After 1:3 PSM,2,148acute STEMI patients were included, with 537 having prior positive FIT and 1,611 without. Patients with prior positive FIT were more likely to have comorbidities such as hyperlipidemia, prior malignancy, post-coronary artery bypass grafting, renal insufficiency, and prior cerebral hemorrhage. The prior positive FIT group had a higher proportion of prior clopidogrel and indobufen usage, while aspirin use during follow-up was lower. Kaplan-Meier analysis demonstrated a significantly higher risk of NACE in acute STEMI patients with prior positive FIT (before PSM: log-rank P = 0.001, after PSM: log-rank P = 0.005, Figure 1）, as well as increased rates of Major Adverse Cardiac and Cerebral Events (MACCE), all-cause death, and gastrointestinal bleeding (log-rank P < 0.05 for all). Multivariate Cox-proportional hazard analysis adjusted for age, sex, percutaneous coronary intervention during hospitalization, diabetes, hypertension, ischemic stroke, atrial fibrillation, medication during hospitalization, and follow-up showed similar results (Figure 2). Conclusions This study reveals a significant association between prior positive FIT and higher rates of NACE, MACCE, all-cause death, and gastrointestinal bleeding in STEMI patients within 1 year. A history of positive FIT results could serve as a prognostic indicator in this specific patient population.

Prevalent and incident anemia in PARAGON-HF

Abstract Background Anemia is a common comorbidity in patients with heart failure (HF) and is associated with adverse prognosis. Renin-angiotensin system inhibitors (RASi) have been shown to lower hemoglobin levels, potentially related to direct reductions in erythropoetin levels and hematopoiesis. We examined whether sacubitril/valsartan might attenuate this effect of RASi alone on incident anemia in patients with HF with mildly reduced or preserved ejection fraction. Methods PARAGON-HF was a global, multicenter randomized clinical trial of sacubitril/valsartan versus the RASi valsartan in patients with HF and left ventricular ejection fraction≥45%. Anemia was defined as hemoglobin <120 g/L in women and <130 g/L in men. We evaluated changes in hemoglobin, risks of incident anemia and new oral iron initiation during follow-up. We also assessed treatment effects on the primary composite endpoint of total HF hospitalizations (HFH) and cardiovascular (CV) death according to anemia status. Results Among 4,795 participants with a hemoglobin measurement available, 1,111 (23.2%) had anemia at randomization of which 3.5%, 77.7%, and 18.8% were characterized as micro-, normo-, and macrocytic anemia. 5.6% were treated with oral iron at baseline. Over a 2.7-year median follow-up period, patients with anemia were at nearly twice the risk of the primary outcome (21.6 vs. 11.5 per 100py; rate ratio 1.90; 95% CI: 1.62-2.21; P<0.001). Compared with valsartan, sacubitril/valsartan significantly slowed the decline in hemoglobin levels by 1.4 g/L (95% CI: 0.4-2.4 g/L; P = 0.005; Figure 1 Panel A). Participants treated with sacubitril/valsartan were at significantly lower risk of developing anemia (30.3% vs. 37.6%; HR 0.76; 95% CI: 0.68-0.85; P<0.001; Figure 1 Panel B) and starting oral iron therapy (8.1% vs. 10.0%; HR 0.81; 95% CI: 0.67-0.97; P = 0.026; Figure 2). Treatment effects of sacubitril/valsartan vs. valsartan on the primary endpoint were consistent among patients with and without anemia (Pinteraction=1.00). Conclusions Among patients with HF with mildly reduced or preserved ejection fraction, treatment with sacubitril/valsartan resulted in slower declines in hemoglobin, lower rates of incident anemia, and fewer new initiations of iron therapy compared with RASi.

Clinical outcomes of immediate complete versus staged revascularization among STEMI patients and multivessel disease without cardiogenic shock: a meta-analysis

Abstract Introduction Multivessel disease in STEMI patients uncomplicated by cardiogenic shock is associated with adverse prognosis and recent evidence support complete revascularization in these patients. However, the optimal timing of non-culprit lesion revascularization is still debated. Methods A literature search from PubMed, Cochrane and Embase databases for relevant RCTs published until December 2023 were conducted. The main outcomes of interests were all-cause mortality, re-infarction, and target vessel revascularization. Results The search yielded 4 randomized controlled trials and the total number of patients included was 1,137 (immediate complete = 571; staged revascularization = 566). Our pooled estimated showed that immediate complete revascularization in STEMI patients and multivessel disease without cardiogenic shock, compared to staged revascularization, was associated with lower rates of re-infarction (OR 0.51, 95% CI 0.27 – 0.98, p < 0.04, I2=22%) and target vessel revascularization (OR 0.54, 95% CI 0.33 – 0.87. p = 0.01, I2=21%), with no significant difference in terms of all-cause mortality (OR 1.22, 95% CI 0.69-2.16, p <0.5, I2=0%). Conclusion In STEMI patients and multivessel disease without cardiogenic shock, immediate complete revascularization is associated with better outcomes in terms of reducing the rate of reinfarction and target vessel revascularization, while there was no significant difference in the outcomes of all-cause mortality between the two groups. These results challenge the current guidelines which favors staged PCI than an immediate complete revascularization approach.Abstract summary poster

Prevalance and impact of concomitant atrial fibrillation in patients undergoing percutaneous coronary intervention for acute myocardial infarction

Abstract Introduction Atrial fibrillation (AF) is a common cardiac arrhythmia associated with coronary artery disease (CAD) and myocardial infarction (MI). The prevalence of AF in patients following acute MI varies, with conflicting evidence on its impact on outcomes. Concomitant atrial fibrillation is associated with an adverse prognosis in patients with acute myocardial infarction (MI). However, it remains unclear whether this is due to a causal effect of AF, or whether AF acts as a surrogate marker for comorbidities in this population Also, there are limited data on whether coronary artery disease distribution impacts the risk of developing AF. Purpose This large cohort study aims to determine the prevalence of AF in acute MI patients treated with PCI, assess its independent prognostic value for MACCE, investigate the association of AF with CAD distribution patterns, and provide insights into the long-term outcomes of AF in this patient population. Methods A cohort of 1000 consecutive MI patients treated with PCI was retrospectively analyzed. Data on demographics, medical history, presentation, treatment, and outcomes was collected. Propensity score matching was used to adjust for baseline differences between AF and non-AF groups. CAD distribution, major adverse events, and MACCE were assessed using statistical analyses. Results Amongst the studied population, 6.5% people had AF (65/1000) and it was noted that those with AF had a worse outcome. However, on statistical analyses (both on multivariable cox and propensity matching) accounting for risk factors, outcomes were not significantly different between those with and without AF. Hence, this negated key baseline differences between AF and non-AF groups, with no significant differences in demographics or presentation. Patients with AF had a higher prevalence of severe CAD in the left main stem (LMS) and left circumflex artery (LCx). The association of AF with MACCE was not significant in the matched groups. Long-term follow-up revealed similar rates of MACCE between AF and non-AF groups. Discussion AF in acute MI patients undergoing PCI is associated with a higher prevalence of severe CAD in the LMS and LCx. AF appears to be a surrogate marker of other risk factors, rather than an independent risk factor for MACCE. The study highlights the need for tailored aggressive treatment for risk factor modification in AF patients with MI. Conclusions AF is associated with an increased risk of MACCE in acute MI patients undergoing PCI. However, this association is primarily driven by the burden of comorbidities associated with AF, emphasizing the importance of tailored treatment strategies for AF patients. Prospective studies with routine ambulatory monitoring are recommended to validate these findings and guide future practice.

Mechanisms affecting the neutrophil to lymphocyte ratio in heart failure: a prospective CMR study

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) is a simple measure of inflammation defined as the ratio of the neutrophils to lymphocytes as measured in the full blood count. It is well known that patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines. It has been demonstrated in a recent meta-analysis that elevated NLR in heart failure is significantly associated with worse outcomes including all-cause mortality, heart failure readmissions and cardiovascular death. Purpose Given this association between NLR and adverse prognosis in HF, we aim to identify which factors are associated with an elevated NLR. This may help to recognise patients at higher risk and guide management. Methods Patients with newly diagnosed HF and left ventricular ejection fraction <50% on referral echocardiogram were prospectively recruited at the time of referral for cardiovascular magnetic resonance (CMR). Exclusion criteria included prior revascularisation, myocardial infarction, anginal chest pain, congenital heart disease and suspected myocarditis. In one appointment patients (N=599) underwent clinical assessment, medication review, full blood count and CMR. The CMR protocol included quantitative assessment myocardial blood flow at stress and rest, assessment of ischaemic and non-ischaemic fibrosis by late gadolinium enhancement imaging and T1 and T2 mapping. Guideline directed medical therapy was determined by the referring physician. Baseline demographic data, medication and MRI results were recorded for all patients. NLR was calculated from full blood count and split into tertiles. Clinical and CMR parameters were compared between tertiles by analysis of variance and chi squared test. Results See Table 1 The factors which were found to be significantly associated with an elevated NLR were age, atrial fibrillation, NTproBNP, diuretic dose, inducible ischaemia and ischaemic fibrosis. Of note there was no significant difference between groups in terms of guideline directed medical therapy use or other CMR parameters. Conclusion NLR is increasingly recognised as a marker of adverse risk in patients with heart failure. This prospective study of 599 heart failure patients with reduced ejection fraction has identified that an elevated NLR is associated with: 1. Evidence of congestion as evidenced by NTproBNP results and increased diuretic doses. 2. Occult coronary artery disease as shown by greater levels of inducible ischaemia and ischaemic fibrosis. These findings suggest that the adverse prognosis associated with elevated NLR in heart failure may be mediated by worsening congestion and occult coronary artery disease. Importantly there was no association between myocardial inflammation or oedema (measured as native T1 and T2) and NLR. Whether NLR improves with medical therapy of heart failure remains to be established and our findings need to be validated in more varied cohorts of patients with heart failure.

Neutrophil-to-lymphocyte ratio can predict the clinical prognosis of patients with primary adosteronism

Abstract Background Excess aldosterone-mediated inflammatory response is thought to be a factor in the high risk of cardiovascular events in patients with primary aldosteronism (PA). Leucocyte related inflammatory parameters, especially NLR, were significantly independent of aldosterone (PAC) in PA patients. However, the impact of NLR on the long-term prognosis of PA patients is unclear. Objective To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) on the long-term prognosis of patients with primary aldosteronism (PA). Methods The data for this study were derived from the Tianjin Health and Medical Big Data Super platform, comprising a retrospective cohort of patients discharged from 72 hospitals in our city from 2010 to 2023. According to the inclusion and exclusion criteria, 570 patients were ultimately included in the statistical analysis. Each patient had laboratory measurements, including blood cell counts, taken after admission and before interventional treatment. The primary endpoint was major cardiovascular events (MACEs), defined as cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. Results During a mean follow-up period of 5 years, 125（21.9%）MACEs were recorded. ROC curve analysis displayed that the best cut-off value of NLR for predicting MACEs was 4.87. The MACEs of the high NLR group at 1 year, 3 years, and 5 years were higher than those of the low NLR group（25.0% vs 9.4%，40.3% vs17.1% 和 40.3% vs 19.3%；P＜0.05).Kaplan-Meier survival curve analysis showed that the survival rate of the low NLR group was higher than that of the high NLR group (P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that NLR was an independent risk factor affecting the prognosis of PA patients, and the difference was statistically significant (P<0.05). Conclusions Elevated NLR is associated with adverse prognosis in patients with PA. NLR can serve as a simple and practical indicator to evaluate the long-term prognosis of PA patients. These findings warrant external validation, preferably in a prospective design.

Development and validation of a prognostic score integrating remote heart failure symptoms and clinical variables for mortality risk prediction after myocardial infarction. The PragueMi score

Abstract Background While heart failure (HF) symptoms are associated with adverse prognosis after myocardial infarction (MI), they are not routinely used for patients’ stratification. Purpose The primary objective of this study was to develop and validate a score to predict mortality risk after MI, combining remotely recorded HF symptoms and clinical risk factors, and to compare it against the guideline-recommended GRACE score. Methods A cohort study design using prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart centre between June 2017 and September 2022 was used. Results Data from 1,135 patients (aged 64±12 years, 26.7% women), were split into derivation (70%) and validation cohort (30%). Components of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) questionnaire and clinical variables were used as possible predictors. The best model included the following variables – age, heart failure history, admission creatinine and heart rate, ejection fraction at hospital discharge, and HF symptoms 1 month after discharge including walking impairment, leg swelling, and change in HF symptoms. Based on these variables, the PragueMi score was developed. In the validation cohort, the PragueMi score showed superior discrimination to the GRACE score for 6 months (AUC 90.1, 95% CI 81.8-98.4 vs. 77.4, 95% CI 62.2-92.5, p=0.04) and 1-year risk prediction (AUC 89.7, 95% CI 83.5-96.0 vs. 76.2, 95% CI 64.7-87.7, p=0.004). Conclusion The PragueMi score combining heart failure symptoms and clinical variables performs better than the currently recommended GRACE score.

Elderly patients with decompensated heart failure: prospective analysis from the LECRA-HF registry

Abstract Background/Introduction Heart failure (HF) presents as a clinical syndrome associated with an adverse prognosis, increased mortality risk, and recurrent hospitalizations for HF (HHF). In Poland, there has been a persistent increase in the overall prevalence and hospitalizations of HF among patients. Each subsequent HHF is associated with progressively worsening prognosis. In Europe, HF is most prevalent in elderly individuals, rendering this patient group particularly susceptible to HF exacerbations. Purpose The aim of this study was to conduct a comprehensive analysis of the oldest patients (≥80 years) hospitalized due to HF decompensation, compared to the rest of the evaluated cohort, including overall mortality after median 46 months of observation. Methods The prospective registry of patients with HF decompensation (LECRA-HF) is an ongoing registry conducted at a tertiary cardiology center specializing in HF treatment. Patients enrolled in the registry (n=1394) were evaluated for the presence of cardiovascular risk factors, HF phenotype, laboratory, and echocardiographic findings, as well as overall mortality. Due to the frequent occurrence of HF in elderly patients, we arbitrarily chose to compare two cohorts of patients: those above (n=306) vs. below 80 years of age (n=1088). Results Median age of elderly patients was 84 [82-86] years, of which only 7.8% were >90 years of age. HFrEF was the most common HF phenotype, which, occurred less frequently in the elderly (54.4 vs 74.4%, P<0.001). In turn, HFpEF was more prevalent in elderly group (39.2 vs 17.7%, P<0.001). Elderly patients were more often female (45.1 vs 30.2%, P<0.001) and had more comorbidities: arterial hypertension (85.6 vs 78.6%, P=0.007), atrial fibrillation (61.1 vs 45.7%, P<0.001), renal failure (49.7 vs 28.5%, P<0.001) as well as peripheral arterial disease (17 vs 9.8%, P=0.005). Those patients had more frequently implanted cardiac pacemakers (28.6 vs 12.6%, P<0.001), but less often implantable cardioverter-defibrillators (7.9 vs 14.3%, P=0.003). During HHF they were less often qualified to elective coronary angiography (24.2 vs 31.5%, P=0.039). At discharge mineralocorticoid receptor antagonist were less often prescribed in that group (42.4 vs 50.3%, P=0.010). During long-term observation patients ≥80 years had a higher all-cause mortality (81 vs 67.4%, P<0.001, Panel A). Moreover, it was also higher elderly with NT-proBNP>4497 pg/mL (P<0.001) and LVEF<41% (P=0.014) (Panel B). Conclusion(s) Patients aged ≥80 years were characterized by a higher burden of comorbidities. They were more often qualified to cardiac pacemakers, but less often to implantable cardioverter-defibrillators and invasive coronary procedures. The most common HF phenotype was HFrEF, however with a significant increase in HFpEF. They exhibited significantly higher overall mortality compared to those <80 years old, which was associated with both LVEF and NT-proBNP levels.

The dynamic increment of epicardial adipose tissue is associated with reverse remodeling after guideline-directed medical treatment in dilated cardiomyopathy patients

Abstract Background/Introduction Epicardial adipose tissue (EAT) accumulation is associated with adverse prognosis in patients with HFpEF and a better prognosis in HFrEF patients. Whether EAT is playing a protective role in dilated cardiomyopathy (DCM) patients have been described sparingly. Purpose Aim to explore whether the epicardial fat would change along with the dynamic changes in cardiac function and volumes after receiving guideline-directed medical therapy (GDMT) in patients with DCM. Methods We prospectively enrolled 232 DCM patients who underwent complete baseline and follow-up Cardiac magnetic resonance (CMR) examinations. The measurement of the epicardial fat composition includes epicardial fat thickness, paracardial fat thickness, and paracardial fat volume, while the measurement of body fat composition includes subcutaneous and visceral abdominal fat, while We used univariable and multivariable logistic regression to evaluate the association between different body and cardiac fat depots with the changes in bi-ventricular structure (delta indexed EDV) and function (delta EF). Results The study included 232 patients (mean age 46.1±14.1 years, 157 (67.7%) males). After GDMT, we found that the visceral fat thickness and EAT (thickness and volume) tend to significantly increase. The increase in the (left ventricular reverse remodeling) LVRR group was significantly higher compared with the non-LVRR group. Independently with the changes of BMI and body fat depots, the increment of EAT was associated with the improvement in bi-ventricular function and volumes (significantly positively correlated with the improvement of LVEF (r = 0.499, p < 0.001), and RVEF (r = 0.482, p < 0.001), negatively correlated with delta LVEDVi (r = -0.407, p < 0.001), delta RVEDVi (r = -0.305, p < 0.001)). Conclusions After GDMT, the increment of EAT was positively correlated with the improvement of bi-ventricular structure and function, independent of the changes in BMI and body fat depots.Graphic Abstract

Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis

Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis. To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis. This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024. Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management. The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months. The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P = .44; between-group difference, -4.82% [95% CI, -15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70]). In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings. ClinicalTrials.gov Identifier: NCT03094143.

Preoperative echocardiography and anesthetic drugs as predictors of post-induction hypotension during general anesthesia: a prospective observational study

Post-induction hypotension (PIH) during general anesthesia is a serious concern due to its high incidence and association with adverse postoperative outcomes and prognosis. We prospectively enrolled consecutive 1,603 patients scheduled for non-cardiac and cardiac surgery under general anesthesia. The primary outcome was defined as the lowest mean blood pressure from induction of general anesthesia to the start of surgery: post-induction blood pressure (PIB). Multivariable regression analysis was used to investigate the relationships between PIB and preoperative echocardiographic measurements, types and doses of anesthetic agents, and preoperative comorbidities and oral medication. Left ventricle regional wall motion abnormality (RWMA) and lower estimated glomerular filtration rate significantly associated lower PIB. Factors significantly associated with higher PIB were high BMI, beta blockers, high pre-induction mean blood pressure, and starting induction in the afternoon. Sevoflurane and prophylactic norepinephrine use were associated with higher PIB as anesthetic interventions. Significant interactions were found between sevoflurane and RWMA (P for interaction: 0.01). This is the first study to demonstrate the feasibility of intervening in the selection of anesthetic agents based on echocardiographic findings and to recommend the use of sevoflurane and prophylactic norepinephrine for the prevention of PIH, especially in patients with RWMA.

Angiotensin-II receptor type 1 and endothelin-1 receptor type A agonistic autoantibodies in patients with STEMI: new kids on the block

Abstract Background The Prognosis after ST-elevation myocardial infarction (STEMI) remains poor. Angiotensin-II and endothelin-1 contribute to adverse prognosis after STEMI through molecular mechanisms that lead to myocardial inflammation, fibrosis and, ultimately, adverse myocardial remodeling. Functional autoantibodies against angiotensin II type 1 (AT1R-AAs) and endothelin-1 type A (ETAR-AAs) receptors bind to the same receptors as natural ligands, eliciting similar (and amplified) responses. In patients with STEMI, AT1R-AAs and ETAR-AAs have been associated with a higher risk of developing microvascular obstruction and left ventricular remodeling. Both microvascular obstruction and left ventricular remodeling are associated with a poor prognosis. Purpose To assess the prognostic role of AT1R-AAs and ETAR-AAs after STEMI. Methods Consecutive STEMI patients who underwent primary percutaneous coronary intervention within 12 h after pain onset were enrolled in this prospective study. The levels of AT1R-AAs and ETAR ETAR-AAs at the time of hospital admission were measured using an enzyme-linked immunosorbent assay (ELISA) in all patients. The incidence of major adverse cardiovascular events (MACE, defined as a composite of cardiovascular mortality, myocardial re-infarction, and hospitalizations for heart failure) during follow-up was the primary outcome. Autoantibody seropositivity was defined according to ELISA’s kit manufacturer’s instructions (levels > 10 U/mL). Results Two hundred patients with STEMI were enrolled. The baseline characteristics of the patients are shown in Table 1. Of these, 110 (55%) were seronegative for both autoantibodies, 44 (22%) were seropositive for one autoantibody (but not both), and 46 (23%) were seropositive for both autoantibodies. The incidence of MACE over a 14-month median follow-up was higher in patients with double (31%) and single (25%) seropositivity than in seronegative patients (13%, p=0.009 and p=0.06, respectively). Survival free from MACE was significantly different across the different degrees of autoantibody seropositivity (Figure 1). In the multivariable Cox regression analysis, adjusted for the variables that were significant in the univariate analysis (highlighted in bold in Table 1), double seropositivity was independently associated with an increased risk of MACE (hazard ratio 2.386, 95 % CI 1.471-3.864, p<0.001). Conclusions The degree of seropositivity for AT1R-AAs and ETAR-AAs is associated with an increased risk of MACE after STEMI. Our findings provide valuable mechanistic insights into the pathophysiology of STEMI and pave the way for future therapies focused on the improvement of long-term prognosis after acute coronary syndromes.

Association of osteopontin and shrunken pore syndrome with hospitalization for renal failure in acute heart failure patients

Abstract Background Shrunken pore syndrome (SPS) emerges as a distinctive manifestation of glomerular filtration dysfunction mainly manifested by the impairment of moderate-sized molecular filtration, distinguished by a variance in renal filtration between cystatin C and creatinine. SPS exhibits correlations with adverse prognosis of various cardiovascular diseases. A decline in renal function correlates with a poor prognosis among individuals with heart failure (HF). Osteopontin (OPN), a protein involved to bone mineralization, has been linked to deteriorating renal function and heightened risk for adverse outcomes in patients with chronic kidney disease. Purpose To explore if OPN and SPS are associated with hospitalization for renal failure in patients with acute HF. Methods Cystatin C and creatinine were analyzed in 395 hospitalized HF patients, of which 324 also had osteopontin (OPN) analyzed using a proximity extension assay. SPS was calculated using the CKD-EPI Equations for Glomerular Filtration Rate and defined as a cystatin C-based estimated glomerular filtration rate (eGFR) <60% of the creatinine based eGFR. Hospitalization for renal failure was extracted from regional registries using ICD10 codes N17-N19. Logistic and Cox regression models were deployed to explore a) OPN’s association with SPS; b) OPN’s association with hospitalization for renal failure; and c) SPS’s association with hospitalization for renal failure, adjusting for age, sex, systolic blood pressure and use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Results The study population had a mean age of 74.8 (±12.0) years, 32.4% were women and 104 (26.5%) patients presented with SPS (Table 1). During the median follow-up period of 71 (interquartile range 56-88) months, 35 (8.9%) patients were hospitalized for renal failure. OPN was associated with the prevalence of SPS (OR 1.66; 95%CI 1.08-2.27; p=0.002), as well as with higher risk of hospitalization due to renal failure (HR 2.71; 95%CI 1.61-4.56; p<0.001). Further, also prevalent SPS was associated with higher risk of hospitalization due to renal failure (HR 2.44; 95%CI 1.14-5.24; p=0.022). Conclusions Here, we demonstrate that higher OPN levels are associated with a higher prevalence of SPS and an elevated risk of hospitalization due to renal failure among patients with HF. Additionally, the presence of SPS was associated with a higher risk of renal failure-related hospitalizations. These findings highlight the potential utility of OPN and SPS as biomarkers for identifying heart failure patients at risk of renal function decline, underscoring the importance of early risk stratification and targeted interventions in this population.

Cardiac structural, functional remodelling, and perfusion impairments across the spectrum of aortic stenosis

Abstract Background Aortic stenosis (AS) accounts for substantial global morbidity and premature mortality even in moderate AS (Mod-AS). Whilst myocardial remodeling response is considered critical in the adverse prognosis of Mod-AS, the precise mechanisms remain poorly understood. We aimed to prospectively assess myocardial remodeling, perfusion and energetics differences in Mod-AS and severe AS (Severe-AS). Methods Fifty-two Severe-AS and 25 Mod-AS patients and 18 demographically-matched controls underwent cardiovascular magnetic resonance and phosphorus-magnetic resonance spectroscopy to define left ventricular (LV) mass and function, global longitudinal shortening (GLS), rest and adenosine-stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR), layer-specific perfusion metrics (subendocardial [Endo], subepicardial [Epi] MBF and MPR, and Endo-Epi-MBF ratio [Endo/Epi]), myocardial scar on late gadolinium enhancement (LGE) imaging, and myocardial energetics (phosphocreatine:ATP ratio [PCr/ATP]). Results Compared to controls, with increasing AS severity, there was progressive increase in LV concentricity (LV mass-index (controls: 46[40,51],Mod-AS:58[51,65],Severe-AS: 70[65,75]g/m2; P<0.0001), and stepwise decline in GLS (controls:19.9[17.6,22.2], Mod-AS:17.7[16.6,18.8], Severe-AS:13.4[12.5,14.4]%; P<0.0001) with significant differences between Mod-AS and Severe-AS in all three comparisons. Both stress MBF(controls:2.1[1.9,2.3],Mod-AS:1.9[1.6,2.2],Severe-AS:1.3[1.2,1.5]ml/min/g; P<0.0001) and MPR(controls:3.3[2.8,3.6],Mod-AS:2.8[2.4,3.2], Severe-AS:1.9[1.8,2.1]; P<0.0001) were only significantly reduced in Severe-AS compared to controls, with significant differences also detected between Mod-AS and Severe-AS. However, stress-endo-MBF (controls:2.0[1.8,2.3], Mod-AS:1.7[1.5,2.0], Severe-AS:1.2[1.1,1.3]ml/min/g; P<0.0001), stress-Endo/Epi(controls:1.00[0.93,1.07],Mod-AS:0.87[0.80,0.94],Severe-AS:0.81[0.75,0.82];P<0.0001), rest-Endo/Epi (controls:1.12[1.10,1.14], Mod-AS:1.06[1.03,1.09], Severe-AS:1.03[1.02,1.06]; P<0.0001) and endo-MPR (controls:3.2[2.7,3.6],Mod-AS:2.5[2.1,2.9],Severe-AS:1.7[1.5,1.8]; P<0.0001) were all significantly reduced in both Mod-AS and Severe-AS. Compared to controls, both AS groups showed significantly lower PCr/ATP (controls:2.2[2.0,2.3],Mod-AS:1.8[1.6,2.0],Severe-AS:1.7[1.6,1.8]; P<0.0001). Only the Severe-AS group had evidence of non-ischemic myocardial scarring on LGE (2.9[0.0,6.2]%), which was detected in 65%(n=34) of patients. AS severity (peak aortic valve velocity) correlated with stress-MBF (r=-0.45, P=0.0003), MPR (r=-0.44, P=0.0005) and GLS (r=-0.47, P=0.0001). Conclusions Moderate and severe-AS are both associated with cardiac concentric hypertrophy, reductions in myocardial energetics, and subendocardial hypoperfusion. Patients with Severe-AS exhibit a more pronounced phenotype with worse LV hypertrophy, contractile dysfunction and myocardial scarring compared to Mod-AS patients.