Type Natriuretic Peptide Research Articles

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0-2

Abstract Background Even in patients with atrial fibrillation (AF) and low CHA2DS2-VASc scores, it is not always possible to completely rule out left atrial appendage (LAA) thrombus. Further stratification of the risk of LAA thrombosis in these patients remains an important yet unresolved issue. Left ventricular hypertrophy (LVH) is a prognostic risk factor in AF and has been associated with a worse prognosis, particularly in those with low CHA2DS2-VASc scores. Purpose To investigate the clinical significance of echocardiographic LVH for risk stratifying LAA thrombogenic milieu as a surrogate for cardioembolic risk in patients with AF and CHA2DS2-VASc scores of 0–2. Methods This was a single-center, retrospective study. We enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0–2 who underwent transesophageal echocardiography. The patients were divided into two groups based on the presence or absence of LVH. Owing to the racial differences in normative left ventricular mass index (LVMI) reference values, LVH was defined in this study using Japanese reference values. LVH was defined as LVMI ≥108 g/m2 for men and ≥98 g/m2 for women. LAA thrombogenic milieu was defined by any of the following findings: (1) thrombus, (2) severe spontaneous echo contrast or sludge, or (3) average LAA flow velocity ≤20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium (LA) were obtained using transthoracic echocardiography. Results The mean age was 61 ± 10 years, and 12.2% were female. Overall, 77 (10.9%) patients were classified into the LVH group, and 41 (5.8%) of patients had LAA thrombogenic milieu. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH (32.5% vs. 2.5%, p<0.001). Figure 1 illustrates the details of the patients with the LAA thrombogenic milieu based on LVH presence and CHA2DS2-VASc scores. The LVH group included six patients with LAA thrombus, even with CHA2DS2-VASc scores of 2, whereas the non-LVH group had no patient with LAA thrombus. Table shows the association of LAA thrombogenic milieu and clinical and echocardiographic parameters by logistic regression analysis; LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and LA volume index). Moreover, LVH provided incremental prognostic value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and LA reservoir strains (p<0.001). These findings are summarized in Figure 2. Conclusion Echocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0–2.

Clinical application of biomarkers in obstructive hypertrophic cardiomyopathy: insights from SEQUOIA-HCM

Abstract Background Multiple studies show that circulating cardiac biomarkers, N-terminal pro-B type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin I (hs-cTnI) are associated with key pathophysiological processes and clinical outcomes in obstructive hypertrophic cardiomyopathy (oHCM). Herein we describe the impact of aficamten on cardiac biomarkers in SEQUOIA-HCM (NCT05186818). Purpose In this pre-specified analysis, we describe associations between baseline NT-proBNP and hs-cTnI concentrations and assess the relationship between changes after treatment with aficamten and trial endpoints. Methods Patients with oHCM in NYHA Class II-III, were randomized 1:1 to 24 weeks of daily aficamten (5–20 mg, n=142) or placebo (n=140). Aficamten dose was adjusted to achieve Valsalva left ventricular outflow tract gradient (LVOT-G) <30 mmHg while maintaining left ventricular ejection fraction (LVEF) ≥50%. Peak oxygen consumption (pVO2) was measured by cardiopulmonary exercise testing at baseline and week 24. Cardiac biomarkers were measured at baseline, each dose titration (weeks 2, 4, and 6), every 4 weeks during treatment and after 4 weeks drug washout. Multivariable regression analysis was used to identify significant predictors of baseline biomarker values. Joint modeling and mediation analysis was used to determine how much of the treatment effect was indirectly mediated by NT-proBNP and hs-cTnI. Results In 282 symptomatic oHCM patients (mean age 59 years, 41% female), the median (IQR) NT-proBNP was 788 ng/L (346, 1699) and hs-cTnI was 12 ng/L (9, 27). At baseline, LVOT-G modestly correlated with NT-proBNP, rho = 0.26 (p<0.001) but not hs-cTnI, rho = 0.06 (p=0.36). Predictors of baseline biomarker values are summarized in Table 1. Compared to placebo, aficamten treatment was associated with an early relative reduction from baseline at week 8 in NT-proBNP (-79% (95% CI -83%, -76%, p<0.001) and in hs-cTnI -41% (-49%, -32%), p<0.001. This magnitude of change persisted to week 24 with biomarker return to baseline after aficamten washout (Figure 1). The mediation analysis suggested that NT-proBNP reduction over the 24-week treatment period reflected 101% (41%, 195%) of aficamten’s effect on pVO2. In contrast hs-cTnI reduction reflected 3% (-18%, 30%) of aficamten’s effect on pVO2. Conclusions Concentrations of NT-proBNP and hs-cTnI are associated with clinically relevant echocardiographic variables in oHCM. Compared with placebo, aficamten treatment markedly reduced plasma NT-proBNP and hs-cTnI concentrations, evident from week 2 and persisting until the end of treatment. NT-proBNP reduction may link LVOT-G with reduced exercise capacity in oHCM. These data support the use of biomarkers as a tool for managing patients with oHCM in order to monitor response to aficamten therapy.Effect of aficamten on biomarkersPredictors of baseline biomarkers

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR <30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT <0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

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

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

Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells.

Hyperuricemia, a prevalent condition, is typically preceded by disturbances in purine metabolism and is frequently associated with hyperlipidemia and other dysfunctions of metabolism. WN1703 demonstrated an inhibitory activity against xanthine oxidoreductase (XOR) that was comparable to febuxostat in our prior investigation. In this study, we assessed the cardiovascular safety of WN1703 in a chronic hyperuricemia rat model induced by potassium oxonate in combination with hypoxanthine. We investigated the changes in cardiovascular biomarkers in chronic hyperuricemia rats treated with febuxostat and WN1703, including creatine kinase (CK), CK-MB, B type natriuretic peptide (BNP), Corin protein (CRN), Neprilysin (NEP), myeloperoxidase (MPO), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8). Additionally, we validated the potential mechanism of cardiac injury induced by WN1703 in H9C2 cells, guided by cardiotoxicity predictions from the cardioToxCSM database and network pharmacology. We observed that excessively rapid urate-lowering, oxidative stress, and inflammation could disrupt myocardial functional homeostasis and increase the risk of cardiovascular injury in hyperuricemia rats, and WN1703 treatment effectively reduced the levels oxidative stress marker 8-OHdG and inflammatory factor TNF-α. Despite the absence of organic damage to the heart with prolonged treatment of febuxostat and WN1703, potential hazard of cardiovascular injury could be associated with the modulation of the TGFβ and RHO/ROCK signaling pathways by febuxostat and WN1703. This could offer new insights into the mechanisms underlying the adverse effects caused by XOR inhibitors.

A-021 Evaluation of a Novel N Terminal Pro B Type Natriuretic Peptide Assay as an aid in the Diagnosis of Acute Heart Failure in the Emergency Department

Abstract Background The signs and symptoms of acute heart failure (AHF) may overlap with other conditions and lead to diagnostic difficulty in the undifferentiated patient with dyspnea. The particularly high negative predictive value (NPV) of natriuretic peptides (NPs) in excluding AHF have rendered these assays especially useful in evaluating dyspnea in acute care setting. This study was conducted to assess the diagnostic performance of a novel N-terminal pro-B type natriuretic peptide (NT-proBNP) assay in the intended use patient population in the emergency department (ED). Methods A multicenter study was conducted in the U.S. on individuals presenting to the ED with dyspnea and a suspicion of AHF. Blood specimens were collected and tested using the Beckman Coulter Access NT-proBNP assay on the DxI 9000 Immunoassay Analyzer. Test results were compared to an adjudicated diagnosis clinical endpoint performed by an independent Clinical Events Committee blinded to the Access NT-proBNP result. Performance included NPV and sensitivity of an age-independent cut point of <300 ng/L to exclude AHF, and the positive predictive value (PPV) of the age-dependent cut points of >450, >900, and >1800 ng/L for ages <50 years, 50-75 years, and >75 years, respectively, for the diagnosis of AHF. The sample size required to achieve a 95% two tailed confidence interval (CI) was 150 subjects per age group to provide clinical performance at 90% (±10%) sensitivity. Sample size was based upon CLSI EP24-A2, Assessment of the Diagnostic Accuracy of Laboratory Tests Using Receiver Operating Characteristic Curves. Sensitivity and specificity were calculated at a series of cutoff points and plotted in separate receiver operation curves (ROC) for an overall age-independent rule-out analysis and for individual age-dependent groups separately. Area under the receiver operator characteristic curve (AUROC) was reported with 95% 2-sided CI. NPV and PPV with respective 95% 2-sided score CI was computed for the overall age-independent cut point and for each age group cohort. Results Of 490 enrolled patients, 41% were adjudicated with AHF with a median (Q1, Q3) age of 60 (47-76) years, and distributions of 46.1% female, 60.8% White and 38.2% Black. The assay had an AUROC for AHF of 0.88 (P<0.001), comparable to other commercially available NT-proBNP assays. The rule-out cut point of <300 ng/L had 96% sensitivity and NPV of 95%. Age-dependent cut points had sensitivity of 84%, 90%, and 87%, specificity of 81%, 70% and 61%, and PPV of 72%, 62%, and 74%, respectively. Conclusions The Access NT-proBNP assay demonstrated high clinical performance in the diagnosis and exclusion of acute HF in the undifferentiated dyspneic patient population and performed similarly well to validated assays used in current clinical practice. Given the continued increase in importance and reach of natriuretic peptide testing, these results are useful to extend availability of this assay to a larger audience.

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0–2

BackgroundThe clinical significance of echocardiographic left ventricular hypertrophy (LVH) in risk stratification of left atrial appendage (LAA) thrombogenic milieu, as a surrogate for cardioembolic risk, in patients with atrial fibrillation (AF) and HA2DS2-VASc scores of 0–2 is unknown. Methods and resultsWe enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0–2 who underwent transesophageal echocardiography. LAA thrombogenic milieu was defined as the presence of a thrombus, severe spontaneous echo contrast, sludge in the LAA, or LAA flow velocity ≤ 20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium were obtained using transthoracic echocardiography. Among the 707 patients, 77 (10.9 %) exhibited LVH. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH group (32.5 % vs. 2.5 %, p < 0.001). LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and left atrium volume index) (odds ratio [OR]: 7.54, 95 % confidence interval [CI]: 3.49–16.29, p < 0.001 and OR: 7.16, 95 % CI: 3.26–15.73, p < 0.001, respectively). Moreover, LVH provided incremental value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and left atrium reservoir strains (p < 0.001). ConclusionEchocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0–2.

Evaluation of potential novel biomarkers for feline hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in cats. The diagnosis can be difficult, requiring advanced echocardiographic skills. Additionally, circulating biomarkers (N-terminal pro-B type natriuretic peptide and cardiac troponin I) have several limitations when used for HCM screening. In previous work, we identified interleukin 18 (IL-18), insulin-like growth factor binding protein 2 (IGFBP-2), brain-type glycogen phosphorylase B (PYGB), and WNT Family Member 5 A (WNT5A) as myocardial genes that show significant differential expression between cats with HCM and healthy cats. The products of these genes are released into the circulation, and we hypothesized that IL-18, IGFBP-2, PYGB, and WNT5A serum RNA and protein concentrations differ between healthy cats, cats with subclinical HCM, and those with HCM and congestive heart failure (HCM + CHF).Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) and enzyme-linked immunosorbent assay (ELISA) were applied to evaluate gene and protein expression, respectively, in the serum of eight healthy controls, eight cats with subclinical HCM, and six cats with HCM + CHF. Serum IGFBP-2 RNA concentrations were significantly different among groups and were highest in cats with subclinical HCM. Compared to healthy controls, serum IL-18 and WNT5A gene expression were significantly higher in cats with HCM + CHF, and WNT5A was higher in cats with subclinical HCM. No differences were observed for PYGB.These results indicate that further investigation via large scale clinical studies for IGFBP-2, WNT5A, and IL-18 may be valuable in diagnosing and staging feline HCM.

Ertugliflozin to Reduce Arrhythmic Burden in Patients with ICDs/CRT-Ds

BackgroundSodium–glucose cotransporter 2 inhibitors (SGLT2is) have beneficial pleiotropic effects, contributing to improved cardiovascular and renal outcomes for patients with and without diabetes. The impact of SGLT2is on arrhythmic burden remains largely unexplored through randomized trials.MethodsIn this multicenter, double-blind, randomized, placebo-controlled trial, we investigated the effects of ertugliflozin on arrhythmic burden among patients with heart failure with an ejection fraction less than 50%. All patients had an implantable cardioverter–defibrillator (ICD) with or without a cardiac resynchronization therapy device (CRT-D) and were randomized (1:1) to receive either ertugliflozin 5 mg once daily or placebo. The primary end point was the number of incident sustained (>30 seconds) ventricular tachycardia or ventricular fibrillation events from baseline to week 52. Secondary end points included the total number of non-sustained ventricular tachycardias, appropriate ICD therapies, changes in N-terminal pro-brain–type natriuretic peptide (NTproBNP) levels, and the number of heart failure hospitalizations.ResultsRandomization was prematurely terminated, after class IA guideline recommendations were published for SGLT2is in patients with heart failure regardless of the ejection fraction. The final analysis included 46 patients (11% of the originally planned sample size). The yearly rate of the primary end point was 3.5 (95% confidence interval [CI] 2.8 to 4.4) with ertugliflozin compared with 13.3 with placebo (95% CI 11.8 to 14.8; rate ratio 0.16, 95% CI 0.04 to 0.61; P<0.001). There were no apparent differences in appropriate ICD therapies, hospitalizations, NTproBNP levels, or predefined adverse and serious adverse events.ConclusionsErtugliflozin reduced sustained ventricular tachycardia or ventricular fibrillation events in adults with heart failure and an ICD compared with placebo; however, our trial ended early and thus results should be interpreted with caution. (Funded by Investigator-initiated Studies Program of Merck Sharp & Dohme Corp and Pfizer; EudraCT number, 2020-002581-14; ClinicalTrials.gov number NCT04600921.)

Associations between psychosocial burden and prognostic biomarkers in patients with chronic coronary syndrome: a STABILITY substudy.

To investigate associations between psychosocial burden and biomarkers reflecting pathophysiological pathways in patients with chronic coronary syndrome. Psychosocial (PS) factors were collected from self-assessed questionnaires and biomarkers representing inflammation (high-sensitivity [hs]-C-reactive protein [CRP], interleukin-6 [IL-6], lipoprotein-associated phospholipase A2 [Lp-PLA2]) and cardiac injury/stress (hs-troponin T [hs-TnT], N-terminal pro-B type natriuretic peptide [NT-proBNP]) were measured in 12,492 patients with chronic coronary syndrome in the STABILITY trial. Associations between level of each psychosocial factor (never-rarely (reference), sometimes, often-always) and biomarkers were evaluated using linear models with adjusted geometric mean ratios (GMR). A score comprising four factors ('feeling down', 'loss of interest', financial stress', 'living alone') that previously demonstrated association with cardiovascular (CV) outcome was created, and categorized into three levels: low, moderate and high PS burden. Associations between PS score and biomarkers were evaluated similarly. Greater PS burden was significantly associated with a gradual increase in inflammatory biomarkers (GMR [95% CI] for moderate vs low PS burden; and high vs low PS burden): hs-CRP (1.09 [1.04-1.14]; 1.12 [1.06-1.17]), IL-6 (1.05 [1.02-1.07]; 1.08 [1.05-1.11]), LpPLA2 (1.01 [1.00 - 1.02]; 1.02 [1.01-1.04]) and cardiac biomarkers hs-TnT (1.03 [1.01-1.06]; 1.06 [1.03-1.09]) and NT-proBNP (1.09 [1.04-1.13]; 1.21 [1.15-1.27]). In patients with chronic coronary syndrome, greater psychosocial burden was associated with increased levels of inflammatory and cardiac biomarkers. While this observational study does not establish causal nature of these associations, the findings suggest inflammation and cardiac injury/stress as plausible pathways linking psychosocial burden to an elevated CV risk, that needs to be further explored.

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

IntroductionPersons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown.MethodsIn this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test.ResultsThe median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E’, or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = − 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = − 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = − 0.28; p < 0.001), peak VO2 (rho = − 0.26; p < 0.001), and ratio of minute ventilation/carbon dioxide production (rho = 0.12; p = 0.002). After adjustment for known confounders, the correlation with Physical Activity Scale in the Elderly and overall Kansas City Cardiomyopathy Questionnaire score was no longer significant.ConclusionAmong patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals.Trial registrationARISE-HF, NCT 04083339 Date Registered August 23, 2019.Graphical abstractAbnormal ECHO defined as Myocardial Global Longitudinal Strain < − 16 or left ventricular mass index > 95 for females or > 115 for males or E/e’ >13 or left atrial volume index > 34. †Normal ECHO is defined as the absence of these abnormalities. Low NT-proBNP is defined as < 71 ng/L while high NT-proBNP is defined as ≥ 71 ng/L.

Characteristics and Factors of 30-Day Readmissions after Hospitalization for Acute Heart Failure in China.

Patients with acute heart failure (HF) are at high risk of 30-day readmission. Little is known about the characteristics and associated factors of 30-day readmissions among patients with acute HF in China. We enrolled consecutive patients hospitalized for acute HF and discharged from 52 hospitals in China from August 2016 to May 2018. We describe the rate of 30-day readmission, the time interval from discharge to readmission, and the causes of readmission. We also analyzed the factors associated with readmission risk by fitting multivariate Cox proportional hazards models. We included 4875 patients with a median age of 67 years (interquartile range, 57-75), 3045 (62.5%) of whom were male. Within 30 days after discharge, 613 (12.6%) patients were readmitted for all causes, with a median from discharge to readmission of 12 (6-21) days. Most readmissions were attributed to cardiovascular causes (71.1%) and 60.0% to HF-related causes. Readmission occurred within 14 days of discharge in more than half of the patients (56.4%). Diabetes (hazard ratio [HR]: 1.25, 95% confidence interval [95% CI]: 1.06-1.50), anemia (HR: 1.26, 95% CI: 1.03-1.53), high New York Heart Association classification (HR: 1.48, 95% CI: 1.08-2.01), elevated N-terminal pro-B type natriuretic peptide (HR: 1.67, 95% CI: 1.24-2.25), and high-sensitivity cardiac troponin T (HR: 1.26, 95% CI: 1.01-1.58) were associated with increased risks of readmission. High systolic blood pressure (HR: 0.56, 95% CI: 0.38-0.81) and Kansas City Cardiomyopathy Questionnaire-12 scores (HR: 0.64, 95% CI: 0.44-0.94) were associated with decreased risk of readmission. In China, almost one in eight patients with acute HF were readmitted within 30 days after discharge, mainly due to cardiovascular reasons, and approximately three-fifths of the readmissions occurred in the first 14 days. Both clinical and patient-centered characteristics were associated with readmission.

Point of care estimation of B type natriuretic peptide levels in pediatric patients as a marker of cardiac disease

Point of care estimation of B type natriuretic peptide levels in pediatric patients as a marker of cardiac disease

Association between atrial cardiopathy and stroke severity in acute ischemic stroke

In this hospital-based cross-sectional analytic study, we retrospectively reviewed clinical data of patients with acute ischemic stroke (AIS) between January 2017 and April 2023. Atrial cardiopathy was defined as any presence of the following: left atrial diameter ≥ 52 mm (males) or ≥ 47 mm (females), elevated P-wave terminal force in V1 > 5000 μV ms, or serum N terminal pro B type natriuretic peptide > 250 pg/ml. Initial stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS; moderate-to-severe, ≥ 5; and severe, ≥ 15). Univariate and multivariate binary logistic regression analyses were performed to assess the association between atrial cardiopathy and stroke severity. Among 662 AIS patients (mean age 70 years [interquartile range 61–78], 31.3% women), 303 (45.8%) had atrial cardiopathy. Multivariable logistic regression analysis showed that the presence of atrial cardiopathy was significantly associated with a higher odd of moderate-to-severe stroke (adjusted odds ratio [OR] 2.16, 95% confidence interval [CI] 1.46–3.20, p < 0.001) and severe stroke (adjusted OR 4.89, 95%CI 2.45–9.76, p < 0.001). This association remained significant in a sensitivity analysis excluding those with atrial fibrillation or coronary artery disease. Findings of the current study revealed that the association of atrial cardiopathy was with initial stroke severity independent of atrial fibrillation and was even confirmed in patients without atrial fibrillation; future studies to explore improved stroke prevention strategies for patients with atrial cardiopathy are needed.

Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study.

The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE. In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation. The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P =0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243-5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056-5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792-30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467-8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288-36.484) were independently associated with elevated hs-cTnI. CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Thiol/Disulfide Homeostasis: A New Oxidative Marker in Heart Failure Patients with Preserved Ejection Fraction.

It is suggested that myocardial dysfunction in heart failure patients may result from increased oxidative stress-related membrane changes. Thiol/disulfide homeostasis is a new oxidative stress indicator. The aim of this study was to evaluate serum thiol levels and thiol/disulfide homeostasis in patients with heart failure with preserved ejection fraction (HFpEF). Eighty-four overweight patients who applied to our clinic between November 2016 and February 2018 and diagnosed with hypertension and left ventricule concentric hypertrophy with normal systolic function are included in the study. Forty-two patients who were asymptomatic and had normal N terminal pro-B type natriuretic peptide (NT-proBNP) levels (≤125) were in the control group. Forty-two patients who have cardiac failure symptoms and have high NT-roBNP levels (>125) were in the patient group. Native thiol, total thiol, and disulfide values of the patient group are found to be significantly lower than the control group (P =.001; P <.001; P =.041 respectively). There is a statictically significant negative correlation between native thiol, total thiol values, and NT-proBNP. There is a statictically significant negative correlation between native thiol, total thiol values, and carbohydrate antigen 125 (CA-125) values. As far as we know from literature, this is the first study on HFpEF and thiol/disulfide homeostasis. It is found that native, total thiol, and disulfide values are low in HFpEF patients and that there is a negative correlation between native, total thiol values and NT-proBNP, CA-125 values. It can be said that oxidant/antioxidant balance is impaired in patients with HFpEF and that larger, randomized studies are needed in order to use oxidant/antioxidant balance in diagnosis and treatment of HFpEF.

Pretransplant NT-proBNP levels are associated with mortality among lung transplant recipients.

The prognostic significance of pretransplant N-terminal pro-brain (B)-type natriuretic peptide (NT-proBNP) level has not been investigated in lung transplant recipients. The electronic files of 173 patients with chronic lung disease who underwent lung transplantation in 2018-2022 at a tertiary medical center were retrospectively reviewed. Right heart catheterization (RHC) and NT-proBNP determination were performed preoperatively in all cases. Pretransplant demographic, clinical, and laboratory data were compared between posttransplant survivors and nonsurvivors. Correlations of NT-proBNP values with lung function and RHC parameters and all-cause mortality were analyzed. NT-proBNP level correlated positively with mean pulmonary artery pressure (R = 0.51, p < 0.001) and pulmonary vascular resistance (PVR) (R = 0.45, p = 0.0013), and negatively with diffusing lung capacity for carbon monoxide (R = -0.25, p = 0.0017), cardiac index (R = -0.26, p = 0.001), and cardiac output (R = -0.23, p = 0.004). Over a median follow-up time of 23.22 months, 74 patients died. On univariate analysis, mortality was significantly associated with higher log-NT-proBNP (hazard ratio [HR] = 0.54, 95% confidence interval [CI] 1.15-2.05, p = 0.016), older age at transplant registration (HR = 1.033, 95% CI 1.009-1.058, p = 0.0068), higher PVR (HR 1.15, 95% CI 1.07-1.23, p = 0.015), and lower cardiac output (HR = 0.62, 95% CI 0.42-0.92, p = 0.045). On multivariate analysis adjusted for age, sex, and body mass index, mortality significance was maintained only for higher log-NT-proBNP (HR = 1.54, 95% CI 1.12-2.11, p = 0.007). Among lung transplant recipients, pretransplant NT-proBNP levels correlated well with RHC parameters and were strongly associated with posttransplantation mortality. Assessment of NT-proBNP may improve risk stratification of lung transplant candidates.

A Study of Abnormal Echocardiogram Findings in Patients With Chronic Kidney Disease With Reference to Cardiac Biomarkers.

Background Chronic kidney disease (CKD) isprevalent, especially in populations with multiple risk factors, such as undiagnosed and untreated hypertension and diabetes mellitus. Cardiovascular diseases (CVDs) leading to poor quality of life or even death have been noted as an increasing trend among CKD patients. This study aims to use cardiac biomarkers to evaluate their association with abnormal echocardiogram findings in CKD patients, which may allow for the improvement of quality of life with early treatment. Methods and materials This observational, cross-sectional study was conducted on 103 diagnosed CKD patients at the Department of Medicine, Dr. D.Y. Patil Medical College, Hospital, and Research Centre in Pimpri, Pune, from January 2023 to January 2024. Ethical approval was acquired, and written consent was obtained from participants. The study utilised cardiac biomarkers such as N-terminal pro-B type natriuretic peptide (NT-proBNP), troponin I (Trop I), and a radiological tool, transthoracic echocardiography (TTE). All patients with diagnosed stages 3, 4, and 5 CKD between the ages of 18-80 years were included, and the exclusion criteria consisted of patients who had already undergone cardiac interventional procedures or known cases of CVDs. Results In our study, out of 103 participants, the majority were aged between 51 and 60 years (35, 34%). The study had a majority of male participants (76, 73.8%). Major risk factors were considered, noting hypertension in 63 (61.2%) and diabetes mellitus in 81(78.6%). Participants were divided into stages of CKD. Cardiac biomarkers such as NT-proBNP and Trop I levels were assessed in all participants in the different stages of CKD showing elevated levels of NT-proBNP across all stages. Transthoracic echocardiogram (TTE) screening tests were also evaluated for all patients, showing diastolic dysfunction (DD) as the most common finding in stage 3 (5, 41.67%), stage 4 (25, 62.5%), and stage 5 (35, 68.83%), followed by left ventricular hypertrophy (LVH) as a common finding in stage 3 (4, 33.3%), stage 4 (20, 50%), and stage 5 (30, 58.2%) CKD. Furthermore, the association between raised cardiac biomarkers and abnormal echocardiogram findings across the stages of CKD was evaluated, resulting in a statistically significant association with p-values < 0.05. Conclusion This research sheds light on the association between cardiac biomarkers and abnormal echocardiogram findings in CKD patients and helps us determine if there is any added benefit orpredictive value in screening these individuals at different stages of the disease to allow early interventionand improvement in treatment and quality of life.

ACAD9 treatment with bezafibrate and nicotinamide riboside temporarily stabilizes cardiomyopathy and lactic acidosis

Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy. Treatment with high dose bezafibrate and nicotinamide riboside resulted in marked clinical improvement including reduced lactate and NT-pro-brain type natriuretic peptide levels, with stabilized echocardiographic measures. After a long stable period, the child succumbed from cardiac failure with infection at 10.5 months. Therapy was well tolerated. Peak bezafibrate levels exceeded its EC50. The clinical improvement with this treatment illustrates its potential, but weak PPAR agonist activity of bezafibrate limited its efficacy.

PREVALENCE OF WILD–TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS IN ELDERLY SUBJECTS FROM THE GENERAL POPULATION

Abstract Background Wild–type transthyretin cardiac amyloidosis (ATTRwt–CA) affects older adults, and is currently considered as a rare disorder. Objective We investigated for the first time the prevalence of ATTRwt–CA in elderly individuals from the general population. Methods General practitioners from Pisa, Italy, proposed a screening for ATTRwt–CA to all their patients aged 65–90 years, until 1,000 accepted. The following red flags were searched: interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical hallmark of CA, or high sensitivity–troponin T ≥14 ng/L. Individuals with at least one red flag (n=346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. Results Four patients received a non–invasive diagnosis of ATTRwt–CA. All complained of dyspnoea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (grade 3), left ventricular (LV) wall thickening, grade 2 to 3 diastolic dysfunction, and N–terminal pro–B–type natriuretic peptide (NT–proBNP) &amp;gt;1,000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT–proBNP &amp;lt;300 ng/L. The prevalence of ATTR–CA in subjects ≥65 years was calculated as 0.46% (i.e., 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2). Conclusions ATTRwt–CA has a prevalence of 0.46% in elderly subjects from the general population.