Propeptide Research Articles

Associations Between Lead and Cadmium Exposure and Subclinical Cardiovascular Disease in U.S. Adults.

The impact of lead and cadmium exposure on subclinical cardiovascular disease (CVD), indicated by elevated high-sensitivity cardiac troponin (hs-cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) remains uncertain. We analyzed data from participants aged 20 and older, without overt CVD, in the National Health and Nutrition Examination Survey (NHANES; 1999-2004). Elevated lead and cadmium levels were defined as 3.5μg/dL and 1.0μg/L (inductively coupled plasma mass spectrometry) and 3.8μg/dL and 0.9μg/L (atomic absorption spectrometry), respectively. Elevated hs-cTnT was ≥ 19ng/L, and elevated NT-proBNP was ≥ 125pg/mL. Multivariate logistic regression estimated the odds ratios (OR) and 95% confidence intervals (CI) for elevated biomarkers. Among 10,197 participants (mean age 48.8years; 50.3% female), 5.3% had elevated hs-cTnT and 19.4% had elevated NT-proBNP. Elevated blood lead was associated with increased ORs for elevated hs-cTnT (OR 1.45, 95% CI 1.15-1.84) and NT-proBNP (OR 1.66, 95% CI 1.40-1.97). The corresponding ORs (95% CI) for elevated blood cadmium were 1.33 (1.02, 1.74) and 1.39 (1.18, 1.65). The effect of elevated blood lead on NT-proBNP was particularly pronounced among non-Hispanic Blacks (OR [95% CI], 3.26 [2.24, 4.74]) compared to Mexican Americans (1.46 [0.99, 2.17]) and non-Hispanic Whites (1.31 [1.02, 1.68]) and was stronger in individuals with impaired kidney function (OR [95% CI], 2.31 [1.43, 3.75]) compared to those with normal kidney function (1.44 [1.18, 1.75]). This study first reveals the association between lead and cadmium exposure and subclinical CVD, underscoring the need for targeted preventive measures to reduce cardiovascular risk and improve health outcomes.

Transcardiac gradients of pro-cholecystokinin, cholecystokinin, and gastrin in patients with and without heart failure with reduced ejection fraction.

Cholecystokinin (CCK) is secreted from the intestines in response to food intake. We previously reported that the CCK gene is also expressed in the mammalian heart, and it has been hypothesized that proCCK could be a novel cardiac biomarker. However, it is not known whether cardiac gene expression leads to secretion in humans. To investigate myocardial secretion of proCCK in patients with heart failure with reduced ejection fraction (HFrEF) or arrythmias. A total of 115 patients undergoing invasive cardiac procedures were included: 55 with HFrEF (67 years [interquartile range (IQR) 60-76], 72% male, LVEF 30% [IQR 20-35]), and 60 without HFrEF (26 with Wolff-Parkinson-White syndrome (WPW) (30 years [IQR 26-39], 61.5% male), and 34 with atrial fibrillation (AFIB) (66 years [IQR 60-71], 61.8% male)). Blood was collected from the coronary sinus (CS) as well as the left atrium or femoral artery (A) to determine the transcardiac concentration gradient (TCproCCK) (CS proCCK concentration - A proCCK concentration). Radioimmunoassays were used for measurements of plasma hormones. TCproCCK across failing hearts was 0.05 pmol/l (IQR: -1.49 to 2.67) (p = 0.365). In non-failing hearts, TCproCCK was 0.35 pmol/l (IQR: -1.57 to 1.29) (p = 0.778) for WPW and 0.68 pmol/l (IQR: -1.58 to 3.28) (p = 0.133) for AFIB. Transcardiac gradients for N-terminal pro B-type natriuretic peptide (NT-proBNP) were observed in all groups. No evidence of net myocardial secretion of proCCK was found in either failing or structurally normal hearts, questioning its proposed role as a cardiac biomarker.

Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re-PHIRE.

Despite receiving guideline-directed medical heart failure (HF) therapy, patients with pulmonary hypertension associated with left heart disease (PH-LHD) experience higher mortality and hospitalization rates than the general HF population. AZD3427 is a functionally selective, long-acting mimetic of relaxin, a hormone that has the potential to induce vasodilation and prevent fibrosis. In a phase 1b study conducted in patients with HF, AZD3427 demonstrated a favourable safety and pharmacokinetic profile. To address the unmet medical need in patients with PH-LHD in the context of HF, AZD3427 is currently under development as a potential treatment option. The Re-PHIRE study is a phase 2b, randomized, double-blind, placebo-controlled, multicentre, dose-ranging study to evaluate the effect of AZD3427 on a broad range of PH-LHD phenotypes. In total, 220 patients will be randomized to four treatment groups to receive a subcutaneous injection of AZD3427 or placebo every 2weeks for 24weeks. The primary endpoint of the study is the change in pulmonary vascular resistance in patients treated with AZD3427 versus placebo after 24weeks of treatment. Key secondary endpoints include changes in mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, 6-min walking distance, N-terminal pro B-type natriuretic peptide levels, echocardiographic parameters, and health-related quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire). Re-PHIRE is the first study of a relaxin mimetic in patients with PH-LHD. The insights gained from the Re-PHIRE study are expected to inform the further development of AZD3427 in the PH-LHD population, including identifying the most suitable pulmonary hypertension and HF phenotypes for treatment.

Effect of trimetazidine on left ventricular functions and cardiac biomarkers in diabetic patients with left ventricular diastolic dysfunction: a randomized controlled trial

We investigated the impact of trimetazidine treatment on left ventricular (LV) functions and cardiac biomarkers in diabetic patients with diastolic dysfunction as an early stage of diabetic cardiomyopathy. Sixty-three patients were randomly assigned to receive either trimetazidine or a placebo for 3 months. At baseline and after 3-months of treatment, measurements of serum levels of glycemic control parameters, lipid profile, tumor necrosis factor alpha, transforming growth factor beta 1, n-terminal pro brain natriuretic peptide and assessment of modified Medical Research Council (mMRC) dyspnea score, echocardiographic indices of LV functions and LV global longitudinal strain (GLS) were performed. After 3-months, trimetazidine group exhibited a significant reduction in left atrial volume index by 6.99% versus an increase by 0.66% in placebo group, p = 0.034. Moreover, average e’ increased by a significantly higher percentage in trimetazidine versus placebo group (8.46 ± 18.64 vs. -2.49 ± 14.52, respectively. p = 0.015). Trimetazidine treatment resulted in a significant increase in LVGLS by 6.66% versus LVGLS reduction by 2.79% in placebo group (p = 0.004). Trimetazidine group had a significantly lower median mMRC dyspnea score compared to placebo (0 vs. 1, respectively, p = 0.015) and a significantly lower low-density lipoprotein (LDL-C) (103.43 ± 28.31 vs. 125.34 ± 45.27, respectively, p = 0.032). There was no significant difference between both groups in levels of other biomarkers. Three-months treatment with trimetazidine improved diastolic function parameters, LVGLS, dyspnea severity and LDL-C levels in diabetic patients with diastolic dysfunction.

Recombinant Klotho administration after myocardial infarction reduces ischaemic injury and arrhythmias by blocking intracellular calcium mishandling and CaMKII activation.

Ischaemic heart disease (IHD) remains a major cause of death and morbidity. Klotho is a well-known anti-ageing factor with relevant cardioprotective actions, at least when renal dysfunction is present, but its actions are much less known when renal function is preserved. This study investigated Klotho as a biomarker and potential novel treatment of IHD-associated complications after myocardial infarction (MI) under preserved renal function. Association between circulating Klotho levels and cardiac injury was investigated in patients after ST-elevation MI (STEMI). Biochemical, in vivo and in vitro cardiac function and histological and molecular studies were performed to determine the effect of recombinant Klotho in the failing hearts of mice after MI. We demonstrated that STEMI patients showed lower systemic Klotho levels, with the lowest Klotho tertile in those patients with higher N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Mice also showed a decrease in systemic Klotho levels after MI induction. Furthermore, recombinant Klotho administration in mice reduced infarct area and attenuated cardiac hypertrophy and fibrosis. We also demonstrated that Klotho treatment prevented reduction in ejection fraction and MI-related ECG changes, including prolonged QRS, JT, QTc, and TpeakTend intervals and premature ventricular contractions. In adult mouse cardiomyocytes, Klotho treatment restricted systolic calcium (Ca2+) release and cell shortening disturbances after MI. Klotho prevented increased diastolic Ca2+ leak and pro-arrhythmogenic events in PMI mice by blocking activation of the Ca2+/calmodulin-dependent kinase type II (CaMKII) pathway, preventing ryanodine receptor type 2 (RyR2) hyperphosphorylation. In conclusion, Klotho supplementation protected against functional and structural cardiac remodelling and ameliorated ventricular arrhythmic events by preventing intracardiomyocyte Ca2+ mishandling in mice following MI. These data uncover a new cardioprotective role of Klotho, emerging as a biomarker of ventricular injury and potential treatment for patients after MI. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

PIN1 prolyl isomerase promotes initiation and progression of bladder cancer through the SREBP2-mediated cholesterol biosynthesis pathway.

Identities of functional pSer/Thr.Pro protein substrates of the PIN1 prolyl isomerase and its effects on downstream signaling in bladder carcinogenesis remain largely unknown. Phenotypically, we found that PIN1 positively regulated bladder cancer cell proliferation, cell motility and urothelium clearance capacity in vitro and controlled tumor growth and potential metastasis in vivo. Mechanistically, we observed a negative enrichment of SREBP2-driven cholesterol metabolism pathways and a decrease in free/total cholesterol levels in PIN1-knockout bladder cancer cells. Moreover, we showed that PIN1 interacted with SREBP2 following its phosphorylation by the JNK MAP kinase at Ser455, which lies near the Site-2 cleavage site that generates the active, nuclear-form of SREBP2. Therapeutically, a combination of the sulfopin PIN1 covalent inhibitor and the simvastatin HMGCoA reductase inhibitor suppressed cell proliferation in vitro and tumor growth in vivo synergistically. Together, these findings emphasize that PIN1 can act as a driver and potential therapeutic target in bladder cancer.

The influence of prolonged aerobic exercise on cardiac, muscular, and renal biomarkers in trained individuals with obesity.

The aim of this study was to investigate the influence of prolonged aerobic exercise on cardiac, muscular and renal inflammatory markers in a group of trained obese men. Seventeen men (aged 40 ± 6years; body mass index [BMI] 31.3 ± 2.8kgm-2, maximal oxygen uptake [V'O2max] 41.5 ± 5.6mlkg-1min-1) ran a half, 30km, or full marathon. Troponin I (cTnI), the n-terminal creatine kinase-myocardial band (CK-MB), pro b-type natriuretic peptide (NT-proBNP), lactate dehydrogenase (LDH), myoglobin, creatinine (CREA) and the estimated glomerular filtration rate (eGFR)were measured before (T0), immediately after (T1) and 3days after the race (T2). The concentrations of cTnI, myoglobin, LDH, CK-MB and CREA significantly increased (P < 0.05), whereas eGRF decreased at T1 (P < 0.05). All the above parameters returned to baseline at T2, except for eGFR, which remained lower than that at T0 (P < 0.05). A positive association was observed between ΔCK-MB (%) and the time spent in Zone 3 during the race (R = 0.686, P = 0.014). The Δmyoglobin (%) was positively correlated with race time, race mean speed and time in Zone 3 (R = 0.574-0.862, P < 0.05). The ∆CREA values were moderately correlated with the race mean HRMAX (%) and time spent in Zone 3 (%) (R = 0.514-0.610; P = 0.05). The ∆eGRF values were moderately inversely correlated with the time spent in Zone 3 (%) (R = - 0.627; P < 0.05). Changes in cardiac, muscular and renal inflammatory markers in trained men with obesity are consistent with those described in the literature in normal-weight individuals. Finally, running parameters, such as running time, average running intensity and time in Zone 3 appear to be responsible for the changes in cardiac, muscular and renal function markers after long-distance running.

Effects of dapagliflozin on heart rate variability, cardiac function, and short-term prognosis in early-onset post-myocardial infarction heart failure.

To investigate the effects of dapagliflozin, in addition to standard therapy, on heart rate variability (HRV), soluble growth stimulation expressed gene 2 protein (sST2), N-terminal pro B-type natriuretic peptide (NT-proBNP), and echocardiographic parameters in patients with early-onset post-myocardial infarction heart failure (HF). A total of 98 patients with early-onset post-myocardial infarction HF were enrolled and randomly divided into a control group (n = 48, receiving standard therapy) and an observation group (n = 50, receiving standard therapy plus dapagliflozin 10 mg daily). HRV, cardiac function, and echocardiographic parameters were measured at baseline and after 24 weeks of treatment. Short-term prognosis and adverse events were also monitored. Compared with the control group, the observation group showed significantly greater improvements in SDNN and SDANN (P < 0.05). Significant improvements were also observed in sST2 and NT-proBNP levels in the observation group compared to the control group (P < 0.05). Additionally, echocardiographic parameters, including EF, LVESD, LVEDD, IVST, LVMI, and E/e', showed greater improvement in the observation group (P < 0.05). The incidence of major adverse cardiovascular events was lower in the observation group (P < 0.05). Multivariate logistic regression model revealed that dapagliflozin use was independently associated with a reduced risk of MACE (OR = 0.265, 95% CI: 0.097-0.724, P = 0.010). Early administration of dapagliflozin 10 mg, in addition to standard therapy, can improve autonomic function, cardiac function, and short-term prognosis in patients with early-onset post-myocardial infarction heart failure.

Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated With Incident Heart Failure Risk

BackgroundHigher soluble urokinase plasminogen activator receptor (suPAR) levels are associated with adverse outcomes in chronic heart failure (HF). ObjectiveWe assessed the association between proteomics-based suPAR levels and incident HF risk in the general population. MethodsIn 40,418 UK Biobank participants without HF or coronary artery disease at enrollment, the association between Olink-based suPAR levels measured as relative protein expression levels and incident all-cause, ischemic, and nonischemic HF was analyzed by competing-risk regression, while accounting for all-cause death as a competing risk. The additional variability in incident HF risk attributable to suPAR levels beyond demographics, traditional risk factors, N-terminal pro B-type natriuretic peptide (NT-proBNP), and CRP was assessed with nested Cox modeling and likelihood ratio testing. ResultsThe mean age was 56 years; 45% were male, and 94% were White. During a median follow-up of 13.7 (IQR 1.5) years, 1,428 (3.5%) incident HF events occurred. Proteomics-based suPAR levels (per 1-SD) were independently associated with incident HF (subdistribution hazard ratio (sHR) 1.37, 95% CI 1.29-1.46), ischemic HF (sHR 1.40, 95% CI 1.28-1.54) and nonischemic HF (sHR 1.32, 95% CI 1.21-1.44) risk, after adjustment for demographics, traditional cardiovascular risk factors, NT-proBNP, and C-reactive protein levels. The addition of suPAR levels to a base risk factor model significantly improved the explained variability of incident HF risk (R2 = 0.76 vs 0.73, P < 0.001). ConclusionsIndependent of demographics, traditional risk factors, NT-proBNP, and C-reactive protein, proteomics-based suPAR levels were significantly associated with incident all-cause, ischemic, and nonischemic HF risk. Proteomics-based measurement of suPAR levels may underestimate the effect size of this relationship.

N-terminal pro brain natriuretic peptide in hepatitis c virus maintenance hemodialysis patients and its relation to diastolic dysfunction and child pugh score

N-terminal pro brain natriuretic peptide in hepatitis c virus maintenance hemodialysis patients and its relation to diastolic dysfunction and child pugh score

Predictive Value of N-Terminal Pro B-Type Natriuretic Peptide for Short-Term Outcome of Cardioversion in Patients with First-Diagnosed or Paroxysmal Atrial Fibrillation Presenting to the Emergency Department.

Background: Atrial fibrillation (AF) is a common arrhythmia in the emergency department (ED). We investigated the role of N-terminal pro b-type natriuretic peptide (NT-proBNP) in predicting both the outcome of AF cardioversion and the risk of AF recurrence or persistence on the 8th (D8) and 30th (D30) day post-cardioversion. Methods: This prospective, observational study evaluated patients with recent-onset AF, managed by either pharmacological (PC) or electrical cardioversion (EC) in the ED. Patients were treated either immediately or electively after 3 weeks of anticoagulation. NT-proBNP assessments were performed prior to cardioversion. Results: Of the 148 patients enrolled, 56% had paroxysmal AF, 85% underwent immediate cardioversion and 72% received EC. Successful cardioversion to sinus rhythm (SR) was achieved in 85% of patients. Patients with successful cardioversion and those who remained free from AF on D8 had lower NT-proBNP levels compared to patients with failed cardioversion or with AF recurrence or persistence on D8 [day of cardioversion, D0: SR vs. non-SR, 387 (127-1095) pg/mL vs. 1262 (595-2295), p = 0.004; D8: SR vs. non-SR, 370 (127-1095) vs. 1366 (718-2295), p = 0.002]. In multivariate analysis, higher logNT-proBNP was associated with higher risk of cardioversion failure [OR, 95%CI: 4.80 (1.58-14.55), p = 0.006] and AF recurrence or persistence on D8 [OR, 95%CI: 3.65 (1.06-12.59), p = 0.041]. ROC analysis confirmed the predictive ability of NT-proBNP for both outcomes (D0: AUC 0.735, p < 0.001; D8: AUC 0.761, p < 0.001). A cut-off value of NT-proBNP > 580 pg/mL was able to predict failure of AF conversion and occurrence of recurrent/persistent AF at D8. Conclusions: NT-proBNP is a promising biomarker for identifying patients presenting to the ED with recent-onset AF who run a greater risk of cardioversion failure and post-discharge AF recurrence/persistence in the immediate and short term.

The distribution of monolignol glucosides coincides with lignification during the formation of compression wood in Pinus thunbergii.

The distributions of monolignol glucosides (MLGs) in compression and opposite woods of Pinus thunbergii were assessed using cryo-time-of-flight secondary ion mass spectrometry to investigate their involvement in lignification. p-Glucocoumaryl alcohol (PG) was identified in the region of the differentiating xylem adjacent to the cambial zone only in compression wood, whereas coniferin (CF) was similarly localized in both compression and opposite woods. Their distribution from the phloem to the xylem was evaluated by high-performance liquid chromatography (HPLC) using serial tangential sections. Variations in storage amounts of CF and PG in the stem of P. thunbergii agreed with lignification stages of the tracheid, supporting the idea that MLGs act as a storage and transportation form of lignin precursors. The imaging of monolignol (ML)-dependent active lignification sites using fluorescence-tagged MLs supported distinct distribution patterns of MLGs for lignification in compression and opposite woods. Methylation-thioacidolysis was applied to compression and opposite wood samples to examine the structural difference between the guaiacyl (G) and p-hydroxyphenyl (H) units in lignin. Most of the H units in compression wood were detected as lignin end groups via thioacidolysis. PG was detected in opposite wood by HPLC; however, the H unit was not detected by thioacidolysis. The differences in ML and MLG distributions, enzyme activity, and resultant lignin structures between the G and H units suggest the possibility of individual mechanisms regulating the heterogeneous structures of G and H unit in lignin.

Iron deficiency and diastolic function in heart failure with preserved ejection fraction

Background. Despite the high prevalence of iron deficiency (ID) in heart failure with preserved ejection fraction (HFpEF), relationship between iron status indicators with the presence of the disease and parameters of diastolic function and myocardial strain have been insufficiently studied.Aim: To evaluate association of iron status indicators with the disease and parameters of diastolic function and myocardial strain in HFpEF patients.Material and Methods. According to diastolic stress test (DST) 67 patients with EF &gt; 50% (65.8 ± 5.5 years) were divided into 2 groups: Gr.1 with HFpEF (n = 41), Gr.2 without HFpEF (n = 26). Parameters of diastolic function, left atrial reservoir strain (LASr), global longitudinal strain (GLS), diastolic reserve as per DST, serum iron (Fe), ferritin, iron transferrin saturation coefficient (ITSC) , hemoglobin (Hb), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), creatinine, estimated glomerular filtration rate (eGFR) were assessed. Spearman method was used to study the relationships between iron status indicators and parameters of diastolic function, LASr, GLS; the cut-off point for ITSC was found by ROC analysis; factors associated with HFpEF were assessed via regression analysis.Results. In group 1, FCII (NYHA) was revealed more frequent with trends to greater prevalence in women, obesity, higher values of peak E, NT-proBNP, CRP &gt; 3.0 mg/ml, lower values of E/e΄, LASr, Hb, ITSC. As per DST, differences between groups in all variables related elevation left ventricular filling pressure were registered; supreme load and heart rate were lowest in Gr1. Anemia was detected in 6 (9%) patients: 5 (12.2%) vs 1 (3.8%), respectively, p = 0.238; Iron deficiency in 27(40.3%): 18 (43.9%) vs 9 (34.6%), p = 0.157. Correlations were defined between Fe and ITSC with supreme load with DST and diastolic function parameters, but not with LASr and GLS. New cut-off point for ITSC = 29.2% (AUC = 0.699, p = 0.009; sensitivity = 71%, specificity = 69%) associated with HFpEF risk (OR 5.029 95% CI 1.575–16.055; p = 0.006) was revealed.Conclusion: Regardless of HFpEF, ID prevailed in patients aged over 60 years old, which determined the necessity of its screening study for the purpose of timely correction. Association between ITSC reduction less than 29.2% and the disease presence was found: risk of having HFpEF concurrently increased by five times. Interactions were registered between Fe and ITSC with supreme load and diastolic function parameters, but not with LASr and GLS. Higher incidence of CRP &gt; 3.0 mg/ml with HFpEF confirmed pro-inflammatory status of the disease.

A Systematic Review and Meta-Analysis of the Safety and Efficacy of SGLT2 Inhibitors in Chronic Heart Failure in ACHD Patients.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have become a first-line therapy for heart failure (HF) in adults. However, data on their use in HF associated with adult congenital heart disease (ACHD) are limited. This systematic review and meta-analysis evaluated the safety, tolerability, and efficacy of SGLT2is in ACHD HF patients, supplementing guideline-directed medical therapy. A comprehensive systematic search and meta-analysis were conducted on studies examining SGLT2i use in ACHD HF patients. The primary endpoint was the change in the New York Heart Association (NYHA) functional class (FC), with secondary endpoints including changes in ventricular function and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Additionally, the safety and tolerability of SGLT2is were evaluated. The meta-analysis included eight studies with 287 patients aged 19-67 years (median age 37.5 years). Adding SGLT2is to combined therapies significantly improved NYHA FC (log odds ratio 1.3, 95% confidence interval [CI] 0.37-2.23, p = 0.01) and reduced NT-proBNP levels (mean difference [MD] -0.43, 95% CI -0.70 to -0.16, p < 0.001). A notable decrease in systolic blood pressure was observed (MD -0.32, 95% CI -0.51 to -0.14, p = 0.00). The adverse effect profile was comparable to that seen in routine HF, with fewer HF hospitalizations post-SGLT2i initiation. Urinary tract infections occurred in 14 patients (5%), with no instances of hypoglycemia or ketoacidosis reported. Medication withdrawal due to adverse effects was noted in 19 patients (7%). SGLT2is are well tolerated in ACHD HF patients. Notably, SGLT2is improved NYHA FC and reduced NT-proBNP levels across a diverse ACHD HF patient cohort. However, further prospective, multicenter studies are needed to confirm the safety and efficacy of SGLT2is in this unique patient population.

Combining cardiac and renal biomarkers to establish a clinical early prediction model for cardiac surgery-associated acute kidney injury: a prospective observational study.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a prevalent complication with poor outcomes, and its early prediction remains a challenging task. Currently available biomarkers for acute kidney injury (AKI) include serum cystatin C (sCysC) and urinary N-acetyl-β-D-glucosaminidase (uNAG). Widely used biomarkers for assessing cardiac function and injury are N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). In light of this, our study aimed to evaluate the effectiveness of these four biomarkers in predicting CSA-AKI. This prospective observational study enrolled adult patients who had undergone cardiac surgery. The clinical prediction model for CSA-AKI was developed using the least absolute shrinkage and selection operator (LASSO) regression method. The model's performance was assessed using the area under the curve of the receiver operating characteristic (ROC-AUC), decision curve analysis (DCA), and calibration curves. Furthermore, a separate validation cohort was constructed to externally validate the prediction model. Additionally, a risk nomogram was created to facilitate risk assessment and prediction. In the modeling cohort consisting of 689 patients and the validation cohort consisting of 313 patients, the total incidence of CSA-AKI was 33.4%. The LASSO regression identified several predictors, including age, history of hypertension, baseline serum creatinine (sCr), coronary artery bypass grafting combined with valve surgery, cardiopulmonary bypass duration, preoperative albumin, hemoglobin, postoperative NT-proBNP, cTnI, sCysC, and uNAG. The constructed clinical prediction model demonstrated robust performance, with a ROC-AUC of 0.830 (0.800-0.860) in the modeling cohort and 0.840 (0.790-0.880) in the validation cohort. Furthermore, both calibration and DCA indicated good model fit and clinical benefit. This study demonstrates that incorporating the immediately postoperative renal biomarkers, sCysC and uNAG, along with the cardiac biomarkers, NT-proBNP and cTnI, into a clinical early prediction model can significantly enhance the accuracy of predicting CSA-AKI. These findings suggest that a comprehensive approach combining both renal and cardiac biomarkers holds promise for improving the early detection and prediction of CSA-AKI.

A Rare Case of Dilated Cardiomyopathy in Sjögren’s Syndrome

Dilated Cardiomyopathy (DCM) is a rare but significant complication in patients with primary Sjögren’s Syndrome (pSS), a systemic autoimmune disease that primarily affects the exocrine glands. Cardiac involvement in pSS is uncommon, making the recognition of DCM in these patients crucial for timely intervention. This is a case of a 44-year-old female with well-controlled hypertension who developed progressively worsening shortness of breath, chest pain and bilateral pedal oedema. She also had a two-month history of dry eyes and dry mouth, indicative of sicca symptoms. Clinical examination revealed signs of fluid overload, a pansystolic murmur and sicca features. Electrocardiogram (ECG) and echocardiography demonstrated severe left ventricular dysfunction with an ejection fraction of 15%, consistent with DCM. Laboratory investigations revealed elevated N-terminal pro b-type natriuretic peptide (NT-proBNP) levels and positive anti-Ro52 and anti-La antibodies, pointing to an autoimmune aetiology. Cardiac Magnetic Resonance (CMR) Imaging confirmed non ischaemic DCM, ruling out ischaemic causes. The patient was diagnosed with DCM secondary to pSS. She was treated with diuretics, Angiotensin Converting Enzyme (ACE) inhibitors and immunosuppressive therapy, including methylprednisolone and a tapering course of prednisolone over six months. Significant clinical improvement was observed on follow-up. This case highlights the importance of recognising autoimmune aetiologies, such as pSS, in patients presenting with unexplained cardiomyopathy. Early diagnosis and interdisciplinary management are essential in preventing severe cardiac complications and improving patient outcomes in rare presentations of Sjögren-associated cardiomyopathy

Pregnancy & cardiovascular disease: the PREG-CVD-HH registry.

Cardiovascular disease (CVD) remains the leading cause of death in pregnant and peripartal women in western countries. Physiological changes during pregnancy can lead to cardiovascular complications in the mother; women with pre-existing heart disease may not tolerate these changes well, increasing their susceptibility to adverse cardiovascular outcomes during pregnancy. The aim of this study is to characterize pregnancy-induced changes in cardiac function, biomarker concentrations and cardiovascular outcomes in women with CVD during pregnancy at a tertiary care hospital in Germany. The PREG-CVD-HH study is a prospective single-center observational study of pregnant women with prevalent CVD treated at the University Medical Center Hamburg, Germany and currently includes 63 women with congenital or acquired heart disease and ten women from the general population included as controls. Participants underwent baseline assessment and dedicated comprehensive echocardiography. Biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP), MR-proadrenomedullin (MRproADM) and high-sensitivity cardiac troponin I (hs-cTnI) were measured serially throughout pregnancy and until 6 and 12 months postpartum. A maternal cardiac event was defined as death due to cardiovascular cause, arrhythmia, heart failure or hospitalization for other cardiac intervention. Mean maternal age was 34 years. A majority had a congenital heart disease (N=41), 10 patients developed pregnancy-associated CVD (e.g., preeclampsia, peripartum cardiomyopathy) and 12 women had known acquired heart disease (e.g., valvular disease, arrhythmia, cardiomyopathy). New-onset heart failure was observed in 14.1% of patients (N=9). Five patients developed arrhythmia and three patients developed preeclampsia. About 21.2% of patients were hospitalized due to cardiovascular events. Death from any or cardiovascular cause did not occur over the study period. Left and right ventricular global longitudinal strain (LV GLS, RV GLS) showed a transient worsening in the third trimester and peripartum period. NT-proBNP ranges broadened during the pregnancy and tended to progressively decrease postpartum in women with CVD. Hs-cTnI levels tended to trend upwards during pregnancy in patients with CVD, however, the hs-cTnI levels remained consistently low throughout pregnancy. In our cohort, pregnancy was associated with a transient increase in cardiac biomarkers and worsening of cardiac function during the third trimester and peripartum. These temporal changes reversed at 6-12 months postpartum, potentially due to decreased cardiac load, fluid shifts and hormonal changes. Overall, data on reference ranges in echocardiographic and biomarker measurements in the pregnant cardiac population are limited and require further investigation. Albeit one third of our cohort was deemed at high and highest maternal risk during pregnancy, there was no maternal death. We recommend that women with CVD receive preconceptional counselling and ongoing management by a specialized "Pregnancy Heart Team" to optimize care and, potentially, maternal outcomes.

The Implication of NT-proBNP in the Assessment of the Clinical Phenotype of Patients with Type 2 Diabetes Mellitus, Without Established Cardiovascular Disease

Background: Natriuretic peptide (NP) levels have been proposed for characterization and risk stratification of heart failure (HF) among patients with cardiovascular disease (CVD). However, their role in patients with diabetes mellitus type 2 (T2DM) has not been well studied and understood. The aim of this study was to assess phenotypical, functional characteristics and imaging parameters in relation to N-terminal pro b-type natriuretic peptide (NT-proBNP) values in T2DM patients without known CVD that may predispose to overt HF. Methods: This was a cross-sectional study of 100 consecutive T2DM patients (mean overall age of 67 ± 9 years, 40% women and 60% men) who were enrolled from the outpatient diabetic clinic. Patients underwent a cardiopulmonary exercise test (CPET), and echocardiographic and cardiac magnetic resonance imaging (CMR); serum NT-proBNP was also measured. Results: The mean (standard deviation) NT-proBNP was 149 (±186) pg/mL. Patients in the highest tertile of NT-proBNP values (&gt;107 pg/mL) had lower values of predicted maximum oxygen consumption compared to the lowest quartile (&lt;55 pg/mL) (84% vs. 92%, p = 0.018) in the CPET and higher ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e′) (9.0 vs. 7.2, p = 0.05) in echocardiography. Finally, there was a negative correlation between right ventricle end diastolic volume in CMR and predicted maximum oxygen consumption (b = −0.225 ± 0.11, p = 0.046). Conclusions: NT-proBNP levels seemed to be a useful marker in people with T2DM, as elevated levels reflected ongoing appearance of HF with preserved ejection fraction and were related to CPET and echocardiographic indices of impaired left ventricular diastolic and right ventricular systolic function.

Efficacy of extracting and preventively intervening late-stage older adults who are at high risk for spending high medical costs by using the health check-up system in Japan: a pilot study.

In Japan, the seven diseases (femur fracture, cerebral infarction, chronic renal failure, heart failure, dementia, pneumonia, and chronic obstructive pulmonary disease) are the top causes of inpatient medical costs among the late-stage older adults aged 75 years and over. This pilot study was conducted with the following two objectives; (1) to examine the proportion of risks of onset and severity of seven diseases among the late-stage older adults, and (2) to examine the efficacy of interventions focusing on the prevention of unplanned hospitalization. Participants were 45,233 older adults aged 75 and over living in Kure City, Japan. In addition to the government-mandated health checkup items, the Intervention group underwent additional risk screening tests included questionnaires, physical examinations, blood tests, and educational guidance by nurses. The efficacy of the intervention was examined whether there were differences in the number of hospitalizations, the use of emergency and critical care, and the incidence of hemodialysis induction between the Intervention and control groups (Usual Health Checkup group and No Health Checkup group) for the 2 years. There were 485 participants in the Intervention group, 1,067 in the Usual Health Checkup group, and 43,712 in the No Health Checkup group. As the risks of seven diseases in the Intervention group, the largest proportion of deviations occurred for systolic blood pressure (63.3%), estimated salt intake (60.3%), and low-density lipoprotein cholesterol (51.5%). Estimated glomerular filtration rate deviated in 41.0%, N-terminal pro b-type natriuretic peptide in 37.9%. 7.5% scored <2 points on the Mini-Cog©, and 9.1% performed the Timed Up and Go test in >12 s. The incidence of hospitalization due to any of the seven diseases was significantly higher in the No Health Checkup group (p < 0.001). There were no differences among the three groups in the use of emergency and critical care or the introduction of hemodialysis. This study revealed that additional health checkup tests and intervention methods could be prevented hospitalization among the adults of 75 years and older. It is necessary to make health checkups and follow-ups more accessible those are already available within the existing health system in Japan.

Characterisation of patients who develop atrial fibrillation-induced cardiomyopathy

IntroductionAtrial fibrillation (AF)-induced cardiomyopathy (AIC) is retrospectively defined after normalisation of left ventricular ejection fraction (LVEF) in sinus rhythm. It is unclear why some patients develop AIC.HypothesisPatients with AIC have...