Terminal Pro-brain Natriuretic Peptide Research Articles

IL-6 and hsCRP predict cardiovascular mortality in patients with heart failure with preserved ejection fraction.

Inflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with HF. We analysed interleukin-6 and hsCRP levels by ELISA and immunonephelometry, respectively, in HFpEF and HFrEF patients referred for coronary angiography and assessed the prognostic value in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. HF was present in 1086 patients (N=506 HFpEF; N=580 HFrEF; mean age 65±10years; 28% female). Increasing IL-6 levels were significantly associated with increased CV mortality in HFpEF [1.5 (95% CI: 1.1-2.2), P=0.018] but not HFrEF [HR 1.3 (95% CI: 1.0-1.7), P=0.06] patients. High-sensitive CRP followed a similar pattern but failed to reach statistical significance after full-adjustment (HFpEF: HR 1.4 95%C I: 1.0-2.0; P=0.065; HFrEF HR: 1.0 95% CI: 0.7-1.3; P=0.800). Interaction analysis in patients stratified by IL-6 and N terminal pro brain natriuretic peptide (NT-proBNP) above and below the median revealed a stepwise increase in CV-mortality in HFpEF (P=0.036) but not HFrEF patients (P=0.220). To investigate the relationship between IL-6 and NT-proBNP, we assessed the genetic IL6-Receptor variant p.Asp358Ala (rs2228145) which is linked to impaired IL-6 receptor signalling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT-pro-BNP levels compared with wildtype carriers (HFpEF 779pg/mL±787 vs. 1180pg/ mL±1532; P=0.008; HFrEF 2289pg/ mL±3439 vs. 2326pg/ mL±3386; P=0.94), raising the hypothesis that IL-6 signalling may play a pathophysiological role in HFpEF. These data suggest a predictive value of elevated IL-6 for CV-mortality in HFpEF but not in HFrEF patients.

Frequency of multi-vessel disease and its association with N Terminal-Pro Brain Natriuretic Peptide Levels among patients with First ST-Elevation Myocardial Infarction.

Frequency of multi-vessel disease and its association with N Terminal-Pro Brain Natriuretic Peptide Levels among patients with First ST-Elevation Myocardial Infarction.

N terminal pro-brain natriuretic peptide level and benefits of chronic total occlusion revascularization

BackgroundThe management of revascularization of chronic total occlusions (CTOs) remains controversial. Whether specific patients gain survival benefit from CTO revascularization remains unknown. ObjectivesWe investigated whether (i) patients with CTO have higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO, (ii) in patients with CTO, NT pro-BNP levels predict adverse events, and (iii) those with elevated levels benefit from revascularization. MethodsIn 392 patients with stable, significant coronary artery disease (CAD) and CTO undergoing coronary angiography, rates of all-cause mortality, cardiovascular death, and a composite (cardiovascular death, myocardial infarction and heart failure hospitalizations) were investigated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP levels and incident event rates in patients with CTO. ResultsNT pro-BNP levels were higher in patients with, compared to those without CTO (median 230.0 vs. 177.7 pg/mL, p ≤0.001). Every doubling of NT pro-BNP level in patients with CTO was associated with a > 25% higher rate of adverse events. 111 (28.5%) patients underwent CTO revascularization. In patients with elevated NT pro-BNP levels (> 125 pg/mL), those who underwent CTO revascularization had substantially lower adverse event rates compared to patients without CTO revascularization (adjusted cardiovascular death hazard ratio 0.29, 95% confidence interval (0.09–0.88). However, in patients with low NT pro-BNP levels (≤ 125 pg/mL), event rates were similar in those with and without CTO revascularization. ConclusionNT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.

Galectin-3 levels and long-term all-cause mortality and hospitalization in heart failure patients: a meta-analysis.

This meta-analysis investigated the dose-response relationship between circulating galectin-3 levels and adverse outcomes in patients with heart failure (HF). PubMed and Embase were screened for studies on galectin-3 and HF. The outcomes of interest were all-cause mortality (ACM), and all-cause mortality or HF-related rehospitalization (ACM/HFR), with a follow-up time of more than 6months. For categorical variables, comparisons between groups with the highest and lowest galectin-3 levels were pooled. For continuous variables, the risks of ACM and ACM/HFR increase per 1-standard deviation (SD) and 1-unit after logarithmic transformation galectin-3 levels were pooled. A random-effects model was employed to calculate the pooled results, and all pooled results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Besides, a dose-response analysis was performed. Twenty-four cohort studies were included. In HF patients, higher circulating galectin-3 levels were significantly associated with a higher risk of long-term ACM (HR, 1.65; 95% CI 1.28-2.13; I2=66%), and 1ng/mL increase in galectin-3 was associated with a 4% (HR, 1.04; 95% CI 1.02-1.06; P=0.002) increase in hazard. Similarly, higher circulating galectin-3 levels were significantly associated with a higher risk of long-term ACM/HFR (HR, 1.52; 95% CI, 1.15 to 2.00; I2=76%), and 1ng/mL increase in galectin-3 was associated with a 3% (HR, 1.03; 95% CI 1.02-1.04; P<0.001) increase in hazard. An increase of 1-SD in galectin-3units was associated with a 29% increased hazard of long-term ACM (HR 1.29; 95% CI 1.13-1.48; I2=42%) and a 22% increased hazard of ACM/HFR (HR 1.22; 95% CI 1.07-1.38; I2=60%). Similarly, an increase of 1-log in galectin-3units was associated with a 98% higher hazard of long-term ACM (HR 1.98; 95% CI 1.48-2.65; I2=41%) and an 83% higher hazard of ACM/HFR in HF patients (HR 1.83; 95% CI 1.02-3.28; I2=7%). Correlation analysis showed a moderate positive correlation between baseline galectin-3 and N terminal pro brain natriuretic peptide levels (r=0.48, P=0.045) and a weak negative correlation with eGFR (r=-0.39, P=0.077). Higher circulating galectin-3 levels after hospitalization of HF patients are linearly and positively associated with the risk of long-term ACM and ACM/HFR.

Abstract 13874: N Terminal Pro-Brain Natriuretic Peptide Levels and Benefits of Chronic Total Occlusion Revascularization

Background: The management of chronic total occlusion (CTO) remains a subject of debate, as the mortality benefit from revascularization remains controversial. Whether specific populations gain a survival benefit from CTO revascularization remains unknown. Purpose: In this prospective study of patients with stable coronary artery disease (CAD), we investigated whether patients with CTO have higher adverse event rates and higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO. We also investigated whether a higher NT pro-BNP level predicts adverse events in patients with CTO and whether those with elevated NT pro-BNP levels have a survival benefit from revascularization. Methods: In 2,253 patients with significant CAD ( &gt; 50% coronary luminal stenosis) undergoing cardiac catheterization, all-cause mortality, cardiovascular mortality and the composite of cardiovascular death, myocardial infarction and heart failure hospitalization rates were evaluated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP level and event rates. Results: Patients with CTO had higher incident event rates by &gt; 20% and had higher NT pro-BNP levels than those without CTO (median 230.0 vs. 177.7 pg/mL, p=&lt;0.001). In patients with CTO, every doubling of NT pro-BNP level was associated with &gt; 25% greater risk of adverse events. In patients with elevated NT pro-BNP level (&gt; 125 pg/mL), CTO revascularization was associated with &gt;50% lower adverse event rates than those without CTO revascularization (adjusted cardiovascular death hazard ratio 0.24, 95% confidence interval 0.07 - 0.81). Among patients with low NT pro-BNP level (&lt; 125 pg/mL), event rates were similar in those with and without CTO revascularization. Conclusion: Patients with CTO have higher adverse event rates than those with significant CAD without CTO. NT pro-BNP levels are higher in patients with CTO and higher levels portend a worse prognosis. Moreover, NT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.

Relationship of atrial fibrillation and N terminal pro brain natriuretic peptide in heart failure patients.

N terminal pro brain natriuretic peptide (NT-proBNP) plays an important role in the diagnosis and prognosis of heart failure (HF). The plasma level of NT-proBNP in atrial fibrillation (AF) patients was higher than of sinus rhythm patients. In HF, NT-proBNP levels are affected by the concomitant presence of AF, making it difficult to distinguish between HF and AF in patients with elevated NT-proBNP. Several other diseases, such as renal failure and pulmonary embolism, are known to further increase NT-proBNP levels in patients with concomitant HF. Therefore, NT-proBNP is a sensitive but non-specific marker for the detection of HF. AF is very important in this regard because among patients with HF regardless of ejection fraction, symptoms such as shortness of breath and atrial enlargement develop and can mimic HF. In the present study, we investigated whether the prognostic value of natriuretic peptides in HF holds true for patients with concomitant AF.

Heart rate variability of acute ischemic stroke patients according to troponin levels

Objective: Neurogenic myocardial stunning is a type of stress-induced cardiomyopathy thought to be a result of dysregulation of the&#x0D; autonomic nervous system. Heart rate variability (HRV) analysis is a potential method for understanding the underlying mechanisms&#x0D; of autonomic dysfunction in ischemic stroke. The aim of the study was to investigate HRV in stroke patients in accordance with&#x0D; troponin levels.&#x0D; Patients and Methods: Sixty-six patients (mean age 65 ± 13 years; 39 male) presenting with acute ischemic stroke were consecutively&#x0D; included. High-sensitive cardiac troponin I (hs-cTnI) levels were accepted as elevated when&gt; 0.04 ng/mL. All patients underwent&#x0D; ambulatory electrocardiographic (ECG) monitoring within the first seven days to obtain time-domain and frequency-domain&#x0D; measures of HRV.&#x0D; Results: Twenty patients (30.3 %) had elevated hs-cTnI. Patients with high troponin levels had significantly lower left ventricular&#x0D; ejection fraction (LVEF), higher ST-segment-T wave changes, and higher N terminal pro-brain natriuretic peptide (NT-proBNP)&#x0D; levels. Low-frequency/high-frequency (LF/HF) value was significantly higher in the troponin-positive group, but other ambulatory&#x0D; ECG monitoring parameters such as SDNN, SDANN, RMSSD, and pNN50 were similar among patients.&#x0D; Conclusion: Neurogenic myocardial damage presenting with high troponin levels can be seen in ischemic stroke patients and may be&#x0D; associated with sympathetic overactivity.

Heart failure risk scores in advanced heart failure patients: insights from the LEVO-D registry.

The prevalence of advanced heart failure (HF) is increasing due to the growing number of patients with HF and their better treatment and survival. There is a scarcity of data on the accuracy of HF web-based risk scores in this selected population. This study aimed to assess mortality prediction performance of the Meta-Analysis Global Group in Chronic HF (MAGGIC-HF) risk score and the model of the Barcelona Bio-HF Risk Calculator (BCN-Bio-HF) containing N terminal pro brain natriuretic peptide in HF patients receiving intermittent inotropic support with levosimendan as destination therapy. Four hundred and three advanced HF patients from 23 tertiary hospitals in Spain receiving intermittent inotropic support with levosimendan as destination therapy were included. Discrimination for all-cause mortality was compared by area under the curve (AUC) and Harrell's C-statistic at 1year. Calibration was assessed by calibration plots comparing observed versus expected events based on estimated risk by each calculator. The included patients were predominantly men, aged 71.5 [interquartile range 64-78] years, with reduced left ventricular ejection fraction (27.5±9.4%); ischaemic heart disease was the most prevalent aetiology (52.5%). Death rate at 1year was 26.8%, while the predicted 1-year mortality by BCN-Bio-HF and MAGGIC-HF was 17.0% and 22.1%, respectively. BCN-Bio-HF AUC was 0.66 (Harrell's C-statistic 0.64), and MAGGIC-HF AUC was 0.62 (Harrell's C-statistic 0.61). The two evaluated risk scores showed suboptimal discrimination and calibration with an underestimation of risk in advanced HF patients receiving levosimendan as destination therapy. There is a need for specific scores for advanced HF.

Assessment of the Clinical Utility of Interleukin-6 in Congestive Heart Failure

Objective: To determine the clinical utility of Interleukin-6 in Congestive heart failure by comparing its association with N terminal-pro brain natriuretic peptide (NT-pro BNP). Study Design: Diagnostic Accuracy Study. Place and Duration: Department of Chemical Pathology, Combined Military Hospital (CMH), Lahore, from 1st September 2022 to 30th November 2022. Methodology: Patients reporting to the CMH Lahore Emergency Department with symptoms suggestive of Congestive Heart Failure (CHF) and Left Ventricular Ejection Fraction (LVEF) &lt; 40% were included in the study after a detailed physical examination. Sample collection was done for analysis of N terminal-pro brain natriuretic peptide and interleukin-6. Standard echocardiography results were obtained from the patients. Their past medical history, the results of the clinical examination, and any additional findings were considered together when evaluating the data for diagnostic reasons. Results: The levels of N terminal-pro brain natriuretic peptide displayed a very weak positive correlation with interleukin-6 (r value=0.016; p value=0.859). Therefore, N terminal-pro brain natriuretic peptide and interleukin-6 were found to have a statistically insignificant association. Interleukin-6 was found to have sensitivity, specificity, and Area under Curve (AUC) (11.11%, 91.18%, and 0.482) respectively at a cut-off level of 65.6pg/ml, for the diagnosis of congestive heart failure. Conclusion: Interleukin-6 has a causative role in the progression and monitoring of congestive heart failure, however; we were unable to show its usefulness as a diagnostic marker of congestive heart failure. The positive correlation of interleukin-6 with N terminal-pro brain natriuretic peptide suggests that interleukin-6 can still be a target for therapeutics. Keywords: Interleukin-6, Diagnostic Accuracy, NT Pro-BNP (Gold Standard), Congestive Heart Failure, Biochemical Markers, Left Ventricular Ejection Fraction. How to Cite This: Saeed M, Rana MZ, Khan N, Anwar H, Awais H, Ahmed S. Assessment of the Clinical Utility of Interleukin-6 in Congestive Heart Failure. Isra Med J. 2023; 15(1): 7-10. DOI: https://doi.org/10.55282/imj.oa1380 This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PLASMA NT-PRO BNP LEVELS IN PREECLAMPTIC AND NORMOTENSIVE HEALTHY PREGNANT WOMEN AND ITS CORRELATION WITH MATERNAL COMPLICATIONS.

Introduction: Preeclampsia (PE) must be detected and diagnosed early to improve the prognosis of both mother and child. Currently, there is no reliable method for predicting and assessing the severity of preeclampsia. With this in mind, the present study evaluated plasma N terminal pro-Brain Natriuretic Peptide (NT-pro BNP) levels in preeclamptic and normotensive women and the correlation between plasma NT-pro BNP levels and maternal complications. Methodology: In this prospective observational study, 100 women were enrolled and divided into a study group and a control group. NT-pro BNP levels were measured at term, just prior to induction of labour, or during early labour. All the women were observed until 48 hours postpartum, and the maternal outcome was recorded and statistically analysed. Results: Substantially elevated serum levels of NT-pro BNP were seen in PE women [437.84±411.12] than in controls [98.89±35.95]. In the control group, none of the women developed any complications, whereas 22 women had 27 complications in the study group. 18.00% of PE women had HELLP (partial), and elevated NT-proBNP levels were 769.84±419.51 pg/ml. Congestive heart failure was observed in only one woman. At the cut-off of 489.84, the Sensitivity and Specicity were 90.00% and 70.00%, respectively, for the diagnostic accuracy of complications in relation to NT-proBNP. A signicantly positive correlation was observed [r=0.6144; p&lt;0.0001*] between the severity of PE and NT-proBNP level. Conclusion: Preeclamptic women have substantially higher NT-pro-BNP levels than healthy women. Hence, NT-proBNP can be used as an indicator for predicting maternal complications.

The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year.

Prolonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up. We conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed. Thirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year. Prolonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis.

Comparison between the Levels of N Terminal Pro-Brain Natriuretic Peptide and Troponin I to Predict Left Ventricular Ejection Fraction in Patients Presenting with First ST-Elevation Myocardial Infarction

Objectives: To compare the levels of N Terminal- ProBrain natriuretic peptide (NT-proBNP) and Troponin I (Trop I) to predict left ventricular ejection fraction (LVEF) in patients presenting with first ST-elevation myocardial infarction (STEMI). Methodology: A cross-sectional study was carried out in Cardiology department of a tertiary care hospital from June to November 2021. A total of 150 patients who presented at emergency department with first STEMI and underwent primary percutaneous coronary intervention (PCI) were included. The patient’s second set of troponin I and NT-proBNP were collected during hospitalization. Echocardiography was done. Left ventricular function was assessed using modified Simpson’s method. For data analysis, SPSS 21 was used. Results: The mean age was 60.60±11.1 years. There were 76% males, 53% hypertensive, 44% diabetic, 14% smokers with the most prominent type of myocardial infarction being anterior wall myocardial infarction accounting for 76.7%. Mean Trop I was 12.2±6.81 ng/ml, 9.5±8.63 ng/ml and 3.0±5.41 ng/ml for LVEF≤40%, 41-49% and &gt;50% respectively while NT-proBNP was 7136.4±7.97pmol/l, 2328.9±3498.6pmol/l and 441±283.6pmol/l for LVEF ≤40%, 41-49%, and &gt;50% respectively. We found a significant mean difference for Trop I (p=0.000) and NT-proBNP (p=0.0001). There was an inverse significant relationship of left ventricular ejection fraction with Trop I (r=-0.290, p=0.000) and NT- proBNP (r=-0.388, p=0.000). Conclusion: In comparison to Troponin I, NT-proBNP serves as a better marker to predict LVEF in patients presenting with first STEMI.

Machine learning in the prediction of cardiac surgery associated acutekidney injury with early postoperative biomarkers.

To establish novel prediction models for predicting acute kidney injury (AKI) after cardiac surgery based on early postoperative biomarkers. This study enrolled patients who underwent cardiac surgery in a Chinese tertiary cardiac center and consisted of a discovery cohort (n = 452, from November 2018 to June 2019) and a validation cohort (n = 326, from December 2019 to May 2020). 43 biomarkers were screened using the least absolute shrinkage and selection operator and logistic regression to construct a nomogram model. Three tree-based machine learning models were also established: eXtreme Gradient Boosting (XGBoost), random forest (RF) and deep forest (DF). Model performance was accessed using area under the receiver operating characteristic curve (AUC). AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Five biomarkers were identified as independent predictors of AKI and were included in the nomogram: soluble ST2 (sST2), N terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid binding protein (H-FABP), lactic dehydrogenase (LDH), and uric acid (UA). In the validation cohort, the nomogram achieved good discrimination, with AUC of 0.834. The machine learning models also exhibited adequate discrimination, with AUC of 0.856, 0.850, and 0.836 for DF, RF, and XGBoost, respectively. Both nomogram and machine learning models had well calibrated. The AUC of sST2, NT-proBNP, H-FABP, LDH, and UA to discriminate AKI were 0.670, 0.713, 0.725, 0.704, and 0.749, respectively. In addition, all of these biomarkers were significantly correlated with AKI after adjusting clinical confounders (odds ratio and 95% confidence interval of the third vs. the first tertile: sST2, 3.55 [2.34-5.49], NT-proBNP, 5.50 [3.54-8.71], H-FABP, 6.64 [4.11-11.06], LDH, 7.47 [4.54-12.64], and UA, 8.93 [5.46-15.06]). Our study provides a series of novel predictive models and five biomarkers for enhancing the risk stratification of AKI after cardiac surgery.

The diagnostic and prognostic value of growth differentiation factor-15 in systemic lupus erythematosus-associated pulmonary arterial hypertension.

Growth-differentiation factor (GDF)-15 is a member of transforming growth factor-β-related cytokine and may respond to right ventricular overload. The objective of this article was to assess the diagnosis and prognostic value of GDF-15 in systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). Serum samples were obtained from 65 patients with SLE-PAH, 51 sex and age matched patients of SLE without PAH (SLE-non-PAH), and 32 healthy controls. Serum GDF-15 level was detected by enzyme-linked immunosorbent assayand the optimal cut-off point was determined by receiver operating characteristiccurve. The primary end-point was death from any cause and the secondary end-point was target goal achievement (TGA). Cox regression analyses and Kaplan-Meier method were performed to identify the prognostic value of GDF-15. Serum GDF-15 levels were significantly higher in SLE-PAH patients (1112.14 ± 781.80 pg/mL) than SLE-non-PAH patients (810 ± 408 pg/mL) and healthy controls (442 ± 139 pg/mL) at baseline. The optimal cut-off value of GDF-15 in the diagnosis of SLE-PAH was 733 pg/mL (AUC = 0.84). In patients with SLE-PAH, GDF-15 level was associated with 6 minwalking distance (ρ = -0.385, p = 0.017) and higher serum N terminal-pro brain natriuretic peptide (NT-proBNP) (ρ = 0.605, p < 0.001). Patients with GDF-15 > 733 pg/mL were more likely to death (adjusted hazard ratio[HR] = 4.01, 95% confidence intervals[CI]:1.23-6.27, p = 0.041) and less likely to achieve treatment goal (adjusted HR = 0.57, 95% CI:0.23-0.79, p = 0.028). In addition, patients with simultaneous elevation of GDF-15 and NT-proBNP showed lower proportion of TGA (p = 0.046). In conclusion, GDF-15 is a new and promising biomarker of development and prognosis in SLE-PAH. The combination of GDF-15 and NT-proBNP may provide more accurate prognostic information.

Increased serum S100A12 levels are associated with higher risk of acute heart failure in patients with type 2 diabetes.

The hyperglycaemic stress induces the release of inflammatory proteins such as S100A12, one of the endogenous ligands of the receptors for advanced glycation end products (RAGE). Chronic activation of RAGE has multiple deleterious effects in target tissues such as the heart and the vessels by promoting oxidative stress, inflammation by the release of cytokines, macrophages infiltration, and vascular cell migration and proliferation, causing ultimately endothelial cell and cardiomyocyte dysfunction. The aim of our study was to investigate the prognostic value of circulating S100A12 beyond established cardiovascular risk factors (CVRF) for heart failure (HF) and major adverse cardiovascular events (MACE) in a cohort of patients with type 2 diabetes. Serum S100A12 concentrations were measured at baseline in 1345 type 2 diabetes patients (58% men, 64±11years) recruited in the SURDIAGENE prospective cohort. Endpoints were the occurrence of acute HF requiring hospitalization (HHF) and MACE. We used a proportional hazard model adjusted for established CVRF (age, sex, duration of diabetes, estimated glomerular filtration rate, albumin/creatinine ratio, history of coronary artery disease) and serum S100A12. During the median follow-up of 84months, 210 (16%) and 505 (38%) patients developed HHF and MACE, respectively. Baseline serum S100A12 concentrations were associated with an increased risk of HHF [hazard ratio (HR) (95% confidence interval) 1.28 (1.01-1.62)], but not MACE [1.04 (0.90-1.20)]. After adjustment for CVRF, S100A12 concentrations remained significantly associated with an increased risk of HHF [1.29 (1.01-1.65)]. In a sub-analysis, patients with high probability of pre-existing HF [N terminal pro brain natriuretic peptide (NT-proBNP) >1000pg/mL, n=87] were excluded. In the remaining 1258 patients, the association of serum S100A12 with the risk of HHF tended to be more pronounced [1.39 (1.06-1.83)]. When including the gold standard HF marker NT-proBNP in the model, the prognostic value of S100A12 for HHF did not reach significance. Youden method performed at 7years for HHF prediction yielded an optimal cut-off for S100A12 concentration of 49ng/mL (sensitivity 53.3, specificity 52.2). Compared with those with S100A12≤49ng/mL, patients with S100A12>49ng/mL had a significantly increased risk of HHF in the univariate model [HR=1.58 (1.19-2.09), P=0.0015] but also in the multivariate model [HR=1.63 (1.23-2.16), P=0.0008]. After addition of NT-proBNP to the multivariate model, S100A12>49ng/mL remained associated with an increased risk of HHF [HR=1.42 (1.07-1.90), P=0.0160]. However, the addition of S100A12 categories on top of multivariate model enriched by NT-pro BNP did not improve the ability of the model to predict HHF (relative integrated discrimination improvement=1.9%, P=0.1500). In patients with type 2 diabetes, increased serum S100A12 concentration is independently associated with risk of HHF, but not with risk of MACE. Compared with NT-proBNP, the potential clinical interest of S100A12 for the prediction of HF events remains limited. However, S100A12 could be a candidate for a multimarker approach for HF risk assessment in diabetic patients.

Synchronized diaphragmatic stimulation for heart failure using the VisONE system: a first-in-patient study.

AimsSynchronized diaphragmatic stimulation (SDS) modulates intrathoracic and intra‐abdominal pressures with favourable effects on cardiac function for patients with a reduced left ventricular ejection fraction (LVEF) and heart failure (HFrEF). VisONE‐HF is a first‐in‐patient, observational study assessing the feasibility and 1 year effects of a novel, minimally invasive SDS device.Methods and resultsThe SDS system comprises a pulse generator and two laparoscopically delivered, bipolar, active‐fixation leads on the inferior diaphragmatic surface. Fifteen symptomatic men with HFrEF and ischaemic heart disease receiving guideline‐recommended therapy were enrolled (age 60 [56, 67] years, New York Heart Association class II [53%] /III [47%], LVEF 27 [23, 33] %, QRSd 117 [100, 125] ms, & N terminal pro brain natriuretic peptide [NT‐proBNP] 1779 [911, 2,072] pg/mL). Implant success was 100%. Patients were evaluated at 3, 6, and 12 months for device‐related or lead‐related complications, quality of life (SF‐36 QOL), 6 min hall walk distance (6MHWd), and by echocardiography. No implant procedure or SDS‐related adverse event occurred, and patients were unaware of diaphragmatic stimulation. By 12 months, left ventricular end‐systolic volume decreased (136 [123, 170] mL to 98 [89, 106] mL; P = 0.05), 6MHWd increased (315 [300, 330] m to 340 [315, 368] m; P = 0.004), and SF‐36 QOL improved (physical scale 0 [0, 0] to 25 [0, 50], P = 0.006; emotional scale 0 [0, 33] to 33 [33, 67], P = 0.001). Although neither reached statistical significance, LVEF decreased (28 [23, 40]% vs. 34 [29, 38]%; P = ns) and NT‐proBNP was lower (1784 [920, 2540] pg/mL vs. 1492 [879, 2028] pg/mL; P = ns).ConclusionsThese data demonstrate the feasibility of laparoscopic implantation and delivery of SDS without raising safety concerns. These encouraging findings should be investigated further in adequately powered randomized trials.

Impact of B-lines-guided intensive heart failure management on outcome of discharged heart failure patients with residual B-lines.

AimsPulmonary congestion (PC) expressed by residual lung ultrasound B‐lines (LUS‐BL) could exist in some discharged heart failure (HF) patients, which is a known determinant of poor outcomes. Detection efficacy for PC is suboptimal with widely used imaging modalities, like X‐ray or echocardiography, while lung ultrasound (LUS) can sufficiently detect PC by visualizing LUS‐BL. In this trial, we sought to evaluate the impact LUS‐BL‐guided intensive HF management post‐discharge on outcome of HF patients discharged with residual LUS‐BL up to 1 year after discharge. IMP‐OUTCOME is a prospective, single‐centre, single‐blinded, randomized cohort study, which is designed to investigate if LUS‐BL‐guided intensive HF management post‐discharge in patients with residual LUS‐BL could improve the clinical outcome up to 1 year after discharge or not.Methods and resultsAfter receiving the standardized treatment of HF according to current guidelines, 318 patients with ≥3 LUS‐BL assessed by LUS within 48 h before discharge will be randomly divided into the conventional HF management group and the LUS‐BL‐guided intensive HF management group at 1:1 ratio. Patient‐related basic clinical data including sex, age, blood chemistry, imaging examination, and drug utilization will be obtained and analysed. LUS‐BL will be assessed at 2 month interval post‐discharge in both groups, but LUS‐BL results will be enveloped in the conventional HF management group, and diuretics will be adjusted based on symptom and physical examination results with or without knowing the LUS‐BL results. Echocardiography examination will be performed for all patients at 12 month post‐discharge. The primary endpoint is consisted of the composite of readmission for worsening HF and all‐cause death during follow up as indicated. The secondary endpoints consisted of the change in the New York Heart Association classification, Duke Activity Status Index, N terminal pro brain natriuretic peptide value, malignant arrhythmia event and 6 min walk distance at each designed follow up, echocardiography‐derived left ventricular ejection fraction, and number of LUS‐BL at 12 month post‐discharge. Safety profile will be recorded and managed accordingly for all patients.ConclusionsThis trial will explore the impact of LUS‐BL‐guided intensive HF management on the outcome of discharged HF patients with residual LUS‐BL up to 1 year after discharge in the era of sodium‐glucose cotransporter‐2 inhibitors and angiotensin receptor blocker‐neprilysin inhibitor.Trial Registration: ClinicalTrials.gov: NCT05035459

Characterization of critically ill patients with septic shock and sepsis-associated cardiomyopathy using cardiovascular MRI.

AimsSepsis‐induced cardiomyopathy is a major complication of septic shock and contributes to its high mortality. This pilot study investigated myocardial tissue differentiation in critically ill, sedated, and ventilated patients with septic shock using cardiovascular magnetic resonance (MR).Methods and resultsFifteen patients with septic shock were prospectively recruited from the intensive care unit. Individuals received a cardiac MR scan (1.5 T) within 48 h after initial catecholamine peak and a transthoracic echocardiography at 48 and 96 h after cardiac MR. Left ventricular ejection fraction was assessed using both imaging modalities. During cardiac MR imaging, balanced steady‐state free precession imaging was performed for evaluation of cardiac anatomy and function in long‐axis and short‐axis views. Native T1 maps (modified Look–Locker inversion recovery 5 s(3 s)3 s), T2 maps, and extracellular volume maps were acquired in mid‐ventricular short axis and assessed for average plane values. Patients were given 0.2 mmol/kg of gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Critical care physicians monitored sedated and ventilated patients during the scan with continuous invasive monitoring and realized breathholds through manual ventilation breaks. Laboratory analysis included high‐sensitive troponine T and N terminal pro brain natriuretic peptide levels. Twelve individuals with complete datasets were available for analysis (age 59.5 ± 16.9 years; 6 female). Nine patients had impaired systolic function with left ventricular ejection fraction (LVEF) < 50% (39.8 ± 5.7%), and three individuals had preserved LVEF (66.9 ± 6.7%). Global longitudinal strain was impaired in both subgroups (LVEF impaired: 11.0 ± 1.8%; LVEF preserved: 16.0 ± 5.8%; P = 0.1). All patients with initially preserved LVEF died during hospital stay; in‐hospital mortality with initially impaired LVEF was 11%. Upon echocardiographic follow‐up, LVEF improved in all previously impaired patients at 48 (52.3 ± 9.0%, P = 0.06) and 96 h (54.9 ± 7.0%, P = 0.02). Patients with impaired systolic function had increased T2 times as compared with patients with preserved LVEF (60.8 ± 5.6 ms vs. 52.2 ± 2.8 ms; P = 0.02). Left ventricular GLS was decreased in all study individuals with impaired LVEF (11.0 ± 1.8%) and less impaired with preserved LVEF (16.0 ± 5.8%; P = 0.01). T1 mapping showed increased T1 times in patients with LVEF impairment as compared with patients with preserved LVEF (1093.9 ± 86.6 ms vs. 987.7 ± 69.3 ms; P = 0.03). Extracellular volume values were elevated in patients with LVEF impairment (27.9 ± 2.1%) as compared with patients with preserved LVEF (22.7 ± 1.9%; P < 0.01).ConclusionsSeptic cardiomyopathy with impaired LVEF reflects inflammatory cardiomyopathy. Takotsubo‐like contractility patterns occur in some cases. Cardiac MR is safely feasible in critically ill, sedated, and ventilated patients using extensive monitoring and experienced staff.Trial Registration: retrospectively registered (ISRCTN85297773)

P108 PLEURAL EFFUSION AND THE POSTERIOR THORACIC WINDOW: ONE MORE CHANCE TO IMAGE THE AORTIC VALVE

Abstract A 85–year–old woman was admitted to our institution with acute respiratory distress. Clinical examination revealed a 5/6 systo–diastolic murmur radiating to both carotid arteries and bilateral lung crackles. Laboratory workup was notable for a N–terminal pro–brain natriuretic peptide (NT–proBNP) of 15.000 ng/L (normal range: &amp;lt; 300 ng/L) and a moderate high–sensitive troponin T elevation of 245 ng/L (normal range: &amp;lt; 14 ng/L) with no increase on serial testing. The hemoglobin and renal function was normal. Evaluation by chest X–ray showed bilateral diffuse pulmonary infiltrates consistent with pulmonary edema and bilateral pleural effusion. The patient was admitted in CCU. A transthoracic echocardiogram was performed bedside, but it was extremely difficult to obtain good quality images from standard view given the ortopnoic decubitus of the patient. However, the aortic valve was heavily calcified and severe aortic stenosis was documented with a mean gradient of 42 mmHg from apical 5 chambers view; 35 mmHg from right parasternal view, with an functional aortic valve area ≈0.6 cm2 (figure, upper panel). Left ventricle shows eccentric hypertrophy and a moderate diffuse reduction of ejection fraction (EF 35–40%). Then, the patient was positioned sitting upright, because the left pleural effusion offered an additional acoustic window—the posterior thoracic window (PTW)—that allowed better alignment of the ultrasound beam with the aortic jet. Mean gradient was recorded definitely higher than from standard view at 50 mm Hg. Moreover, aortic regurgitation that appeared mild from standard view was documented as significant from PTW. In fact, a proper alignment of the aortic regurgitation jet was feasible from this view with a quantification of severity with multiparameter criteria as suggested from the guidelines (PHT 166 ms, Vena contracta 8 mm; Rvol 60 ml). (Figure, lower panel) Conclusion Obtaining adequate echocardiographic images in critically ill patients is important for better diagnosis and treatment. For several reasons, this group of patients remains among the most challenging with regard to quality of echocardiographic images. In presence of pleural effusion and technically difficult echo exams, the PTW should be considered in the assessment of cardiac structures including aortic valve as a potentially useful option to provide further diagnostic information.

Anti-mitochondrial antibodies in Indian patients with idiopathic inflammatory myopathies.

Anti-mitochondrial antibodies (AMAs) are associated with distinct clinical phenotypes including cardiac and hepatic manifestations in idiopathic inflammatory myopathies (IIMs). This article studies the prevalence, clinical characteristics and outcomes of AMA in Indian patients with IIM. Patients (97: 81 adult, 16 juvenile) clinically diagnosed with polymyositis or antibody-negative IIM were retrieved from the MyoCite bio-archive. They were tested for myositis-specific autoantibodies / myositis autoantibodies (MSAs/MAAs) using line immunoassay and antinuclear antibodies and AMAs using immunofluorescence assay (IFA). Patients were also screened for cardiac biomarkers (cardiac troponin I [c-TnI] and N terminal-pro brain natriuretic peptide [NT-pro-BNP] using immunometric immunoassay technique and enhanced chemiluminescence assay testing respectively) and hepatic manifestations using AMA testing. Results were formulated after carrying out analytical tests. Of the cohort, 5 adults (6.2%) (M:F 0:1) with a median age and disease duration of 37 years and 2 months respectively, tested AMA+ while the children tested negative. Dermatomyositis was the commonest phenotype, with amyopathic forms being common, often with MSA positivity. Cancer-associated myositis and polymyositis were also seen. AMA positivity is associated with Gottron's sign and calcinosis. Comparable levels of C-TnI and NT-pro-BNP and AMA testing in patients help to rule out subclinical cardiac and hepatic involvement respectively. Anti-mitochondrial antibodies are rare (6.2%) in different subtypes of IIM in the Indian population, and often coexist with MSAs. Their negative association with cardiac and hepatic involvement and probable association with Gottron's sign and calcinosis merit further investigation and long-term follow-up to understand the entire spectrum of the disease.