Natriuretic Research Articles

Expression and Clinical Implications of pro-BNP and Soluble ST2 in Chronic Heart Failure

Aims/Background Chronic heart failure (CHF) is a complex clinical syndrome resulting from various cardiac diseases, characterized by weakened cardiac pumping capacity and inadequate blood supply to body tissues. This study aims to investigate the expression and clinical implications of pro-B-type natriuretic peptide (pro-BNP) and soluble suppression of tumorigenicity 2 (sST2) in CHF to explore their potential in early diagnosis and severity assessment of the pathological condition. Methods This study included 146 CHF patients treated at our hospital from January 2022 to December 2023, who were classified in the observation group, and 150 concurrent healthy people categorized in the control group. pro-BNP and sST2 levels in the observation and control groups were compared. The diagnostic value of pro-BNP and sST2 in CHF was determined using receiver operating characteristic (ROC) curves. Besides, pro-BNP and sST2 levels in patients with different New York Heart Association (NYHA) grades were compared, and their relationships with left ventricular ejection fraction (LVEF), left atrial diameter (LAD), and left ventricular end-diastolic diameter (LVEDD) were assessed by means of Pearson's correlation. Results CHF cases showed markedly higher pro-BNP and sST2 levels than healthy controls (p < 0.05). The area under the ROC curves for pro-BNP and sST2 in diagnosing CHF was 0.826 (95% CI: 0.778–0.875) and 0.733 (95% CI: 0.674–0.791), respectively. pro-BNP and sST2 levels were similar in grades I and II patients (p > 0.05), but lower when compared with those in grades III and IV patients (p < 0.05). Grade III patients showed lower pro-BNP and sST2 expression than grade Ⅳ patients (p < 0.05). Additionally, pro-BNP and sST2 had an inverse connection with LVEF (r = –0.764 and r = –0.535, respectively) and a positive correlation with LAD (r = 0.752 and r = 0.535, respectively) and LVEDD (r = 0.721 and r = 0.544, respectively). Conclusion pro-BNP and sST2 exhibit good diagnostic value for CHF, owing to their close association with patients' cardiac function. These biomarkers can be used as effective indicators to evaluate the severity of heart failure.

Development of cancer therapy-related cardiac dysfunction in anthracycline-treated breast cancer patients: a retrospective study

PurposeCardiac dysfunction as a result of anthracycline treatment is a major concern regarding the management of patient life after therapy. The aim of the present study was to determine the clinical characteristics of cancer patients at high risk of developing cancer therapy-related cardiac dysfunction (CTRCD), in order to improve the risk management for the appropriate treatment.MethodsThis is a single-center, retrospective study of patients with breast cancer who underwent anthracycline treatment and had regular consultations with cardiologists. To investigate the incidence of CTRCD and the risk factors related to its occurrence, left ventricular ejection fraction (LVEF), cardiac troponin I (TnI), and brain natriuretic peptide (BNP) were assessed in 177 patients at the start of anthracycline treatment, and again at 3, 6, 9, and 12 months.ResultsEight patients (4.5%) developed CTRCD (CTRCD group). The comparisons between the CTRCD group and those without CTRCD (non-CTRCD group) showed significant differences in pre-treatment cancer stage and neutrophil/lymphocyte ratio (NLR). Multivariate analysis showed a strong association between pre-treatment cancer stage, NLR, and type of anthracycline administered (epirubicin or doxorubicin).ConclusionHigh NLR, the more advanced stages of cancer, and doxorubicin administration were suggested as possible risk factors for the development of CTRCD. Special attention should be warranted for patients with any of these risk factors.

Association between NT-proBNP levels and risk of atrial fibrillation: a systematic review and meta-analysis of cohort studies

Background and aimsN-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in clinical practice, particularly for heart failure, but its role in predicting atrial fibrillation (AF) risk is not fully...

Clinical manifestations and misdiagnosis factors of pulmonary embolism patients seeking treatment in cardiology.

To explore the clinical manifestations and factors leading to misdiagnosis in pulmonary embolism (PE) patients in a cardiology department. We retrospectively analyzed 74 patients diagnosed with PE at our hospital from March 2018 to March 2022, comparing them to 136 patients suspected of PE but excluded by computed tomography pulmonary angiography during the same period. Both groups received the same basic care, including disease counseling, nutritional planning, and monitoring. We compared general information, clinical manifestations, risk factors, and auxiliary examinations to identify correlations between specific manifestations and misdiagnosis factors. The male-to-female ratio in the PE group was approximately 3:4, which was statistically significant compared to the control group (P < .05), though its impact on PE incidence was low. Common symptoms in the PE group included chest tightness, shortness of breath, sweating, and chest pain, with no significant difference from the control group (P > .05). Notable risk factors included deep vein thrombosis (DVT) (43.24%), prolonged bed rest (32.43%), lower limb varicose veins (18.92%), trauma (21.62%), pulmonary infections (62.16%), coronary heart disease (37.84%), respiratory failure (32.43%), and chronic obstructive pulmonary disease (13.51%). DVT was significantly associated with PE (P < .05). Multivariate logistic regression identified DVT (OR = 118.528, 95% CI: 6.959-2018.906, P = .001) and lower limb varicose veins (OR = 212.766, 95% CI: 6.584-6875.950, P = .003) as independent predictive factors for suspected PE. Clinical manifestations strongly correlated with PE included pulmonary rales, cyanosis, tachycardia, hypotension, elevated D-dimer, positive N-terminal pro-brain natriuretic peptide, and sinus tachycardia on echocardiogram. PE in cardiology patients may present with pulmonary rales, hypotension, shortness of breath, and abdominal symptoms, warranting reexamination for PE. Misdiagnosis factors typically involve chest pain, tightness, and shortness of breath. Lower limb varicose veins and DVT are reliable predictors of suspected PE.

Diagnosis and management of a more advanced stage of preclinical myxomatous mitral valve disease in dogs without echocardiography.

Myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs. Appropriate diagnosis and staging can be performed by means of an echocardiographic examination. Early disease stages might be accompanied by valvular insufficiency and, in more advanced phases, by cardiac dilatation. A correct diagnosis of this preclinical phase and identification of cardiac enlargement should be carried out in order to advise appropriate medical treatment. When echocardiography is not available or declined by the dog's owners, alternative methods to identify the disease and predict clinically relevant cardiomegaly, can be performed. Among these, cardiac auscultation and assessment of heart murmur intensity, cardiac dimensions obtained by thoracic radiography, by means of vertebral heart size, and cardiac biomarkers, in particular N-terminal pro-B-type natriuretic peptide (NT-proBNP), can be carried out as single tests or in combination, in order to identify dogs with increased risk of congestive heart failure, and needing an early treatment with pimobendan. In particular, a heart murmur intensity ≥3/6 (moderate or louder), a vertebral heart size ≥11,5 units obtained from a latero-lateral thoracic radiographic view, and plasma concentrations of N-terminal pro-B-type natriuretic peptide value > 1100 pmol/l, are findings that might suggest presence of clinically relevant cardiomegaly with a good specificity. A practical algorithm to guide clinicians in managing dogs with suspicion of valvular disease has been created, starting from clinical examination, and using the aforementioned additional tests in order to advise the appropriate controls and therapy.

Atypical presentation of Andersen-Tawil syndrome: heart failure with reduced ejection without periodic paralysis or dysmorphic features

Background: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder caused by variants in the KCNJ2 gene. It is associated with periodic paralysis, dysmorphic features and cardiac arrhythmias. The syndrome exhibits incomplete penetrance, leading to a broad spectrum of clinical manifestations, making diagnosis challenging. Case description: A male in his mid-20s with class 3 obesity presented to the emergency department with a week-long history of worsening chest pain, orthopnoea and fatigue. His family history was significant for sudden cardiac death affecting both his mother and brother, with his father having died from complications of Wolff-Parkinson-White syndrome. Cardiovascular examination revealed an S3 heart sound and elevated brain natriuretic peptide levels at 875 pg/ml, with undetectable troponins; potassium level on admission was 3.6 mEq/l. An electrocardiogram showed normal sinus rhythm, first-degree heart block, left atrial enlargement, left bundle branch block and a prolonged QTc of 486 ms. A transthoracic echocardiogram demonstrated a 15-20% reduction in ejection fraction with global left ventricular hypokinesis and left atrial enlargement. Ultimately, he was diagnosed with non-ischaemic dilated cardiomyopathy and referred for genetic testing, which revealed a KCNJ2 variant. Shortly after discharge, he experienced a 55-second run of ventricular tachycardia, necessitating the placement of a single-chamber ICD. Currently, the patient remains on guideline-directed medical therapy and is listed for a heart transplant. Conclusions: Dilated cardiomyopathy, although a rare manifestation in ATS, can profoundly increase the risk of fatal arrythmias, necessitating the need for a low threshold of suspicion, to ensure timely diagnosis and management.

Mitral valve transcatheter edge-to-edge repair in the elderly-A safe and effective therapy.

Prevalence of mitral regurgitation (MR) and comorbidity burden rise with age. Mitral valve transcatheter edge-to-edge repair (M-TEER) is increasingly performed in elderly patients, but only limited data are available for this specific subgroup. In this study, outcomes of octogenarians and nonagenarians undergoing M-TEER were analysed using a large real-world dataset. This retrospective study included consecutive patients undergoing M-TEER at the Ulm University Heart Center between January 2010 and December 2021. The cohort was divided into an elderly group and a younger group based on the cohorts' median age. Group differences regarding 1 and 3year mortality and heart failure hospitalization rates were assessed using Kaplan-Meier survival analysis and Cox proportional hazard models. A total of 1118 patients [median age 79 (inter-quartile range 74-83) years; 42% female] were included and divided into 513 elderly (≥80years) and 605 younger (<80years) patients. Primary MR was more frequent in the elderly group (56% vs. 27%, P<0.001). Pre-procedural and post-procedural MR grades were comparable between groups (pre-procedural MR grade 4: 69% in the elderly group vs. 71% in the younger group, P=0.67; post-procedural MR grade 1: 60% in the elderly group vs. 58% in the younger group, P=0.77) as well as in-hospital mortality rates (0.2% vs. 0.3%, P=0.66). Three-year heart failure hospitalization rates did not differ significantly between both groups (30.7% in the older age cohort vs. 36.0% in the younger cohort, P=0.191). While 1year all-cause mortality rates were comparable (18% vs. 16.4%, P=0.577), 3year all-cause mortality was significantly higher in the elderly [43.1% vs. 33.0%; hazard ratio (HR) 1.29 (95% confidence interval 1.02-1.65), P=0.035]. Pre-procedural N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥3402pg/mL [HR 2.29 (95% CI 1.34-3.90), P=0.002], pre-interventional MR grade [HR 1.79 (95% CI 1.01-3.17), P=0.045] and European System for Cardiac Operative Risk Evaluation (EuroSCORE) II [HR 1.06 (95% CI 1.03-1.08), P<0.001] were identified as independent predictors of 3year mortality in the elderly. M-TEER displays a safe and effective treatment option for elderly patients with symptomatic MR, offering symptom relief and comparable 1year outcomes to younger patients. Elderly patients with elevated EuroSCORE II and advanced heart failure might benefit from additional care to further reduce 3year mortality.

Proteomics in Acute Heart Transplant Rejection, On Behalf of the GRAfT Investigators.

Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets. Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate. Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR). Differential expression was found in 2 proteins during ACR (inflammatory proteins CXCL10 and CD5) and 73 proteins during AMR. The most abundant AMR proteins were the heart failure biomarkers N-terminal pro-B-type natriuretic peptide and suppression of tumorigenicity 2. In univariate logistic regression, odds of identifying ACR on endomyocardial biopsy increased with doubling of CXCL10 (odds ratio [OR] 2.2 [95% confidence interval (CI), 1.3-3.6]) and CD5 (OR 4.7 [95% CI, 1.7-12.9]) concentrations, and odds of AMR increased with doubling of N-terminal pro-B-type natriuretic peptide (OR 13.0 [95% CI, 2.7-62.7) and suppression of tumorigenicity 2 (OR 4.8 [95% CI, 2.1-10.7]) concentrations. After multivariable analysis with clinical covariates, these proteins showed similar odds of ACR or AMR on biopsy. Pathway analysis identified T cell-receptor signaling and cell differentiation as key pathways in ACR and cardiovascular disease and cell turnover in AMR. Proteomic analysis reveals unique biomarkers and biological pathway expression in ACR and AMR. Cardiac injury-associated biomarkers were more pronounced in AMR, whereas inflammatory biomarkers were more pronounced in ACR. Proteomic analysis may provide insights into rejection pathophysiology, detection, and therapy.

The effect of trimetazidine on cardiac haemodynamics and mitochondrial function in wild-type transthyretin amyloidosis.

Wild-type transthyretin cardiac amyloidosis (ATTRwt) is a cardiomyopathy causing myocardial hypoperfusion and impaired cardiac mitochondrial function. Trimetazidine is an antianginal agent used in patients with stable angina pectoris, which improves cardiac contractility and mitochondrial function. The aim of the study was to investigate the effect of trimetazidine on invasive haemodynamics and cardiac mitochondrial function in ATTRwt. In a randomized, double-blind, placebo-controlled, crossover trial, 22 patients with ATTRwt received 4weeks of trimetazidine and placebo in randomized order. After each treatment period followed examinations with endomyocardial biopsies taken for high-resolution respirometry and right heart catheterization at rest and during a cardiopulmonary exercise test. The primary endpoint was mean pulmonary artery wedge pressure (mPAWP) during peak exercise. The secondary endpoint was cardiac mitochondrial oxidative phosphorylation capacity. Exploratory endpoints were echocardiographic parameters, cardiac biomarker levels and quality of life. Trimetazidine did not significantly reduce mPAWP during peak exercise (31±12 vs. 31±13mmHg, P=0.61) or improve the cardiac mitochondrial oxidative phosphorylation capacity (73.4±7.7 vs. 75.3±7.7pmol O2/(mg*s), P=0.81) compared with placebo, nor did treatment with trimetazidine improve ejection fraction (P=0.93), global longitudinal strain (P=0.23), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P=0.92) or the patients' quality of life (P=0.98). In ATTRwt, treatment with trimetazidine did not improve mPAWP or cardiac mitochondrial oxidative phosphorylation capacity compared with placebo.

Clinical characteristics and in-hospital event rate of chronic obstructive pulmonary disease patients with concurrent acute myocardial infarction

This study was to investigate the clinical features of chronic obstructive pulmonary disease (COPD) patients with concurrent acute myocardial infarction (AMI) and analyze the occurrence of in-hospital adverse events. Patients with AMI who were admitted to Beijing Chaoyang Hospital from January 2019 to August 2023 were retrospectively collected. All patients were divided into COPD with concurrent AMI group and simple AMI group according to whether they were with concurrent COPD. All patients received interventional treatment for AMI. The clinical features and the occurrence of in-hospital adverse events were compared between the two groups. A total of 183 AMI patients aged (65.6±13.6) years were enrolled, including 142 males (77.6%). There were 94 patients (51.4%) in simple AMI group and 89 patients (48.6%) in COPD with concurrent AMI group, respectively. Patients in COPD with concurrent AMI group were older, had higher Killip grade, rate of smoking and previous percutaneous coronary intervention history, creatinine and B-type natriuretic peptide levels, and lower albumin, hemoglobin, low-density lipoprotein cholesterol, white blood cell count and cardiac troponin I than those of simple AMI group (all P<0.05). There were no significant differences in echocardiographic parameters between the two groups (all P>0.05). The proportion of β-blockers, angiotensin-converting enzyme inhibitors/angiotensin-blockers used in COPD with concurrent AMI group was lower (P<0.05). Patients in COPD with concurrent AMI group had longer length of hospital stay than those in simple AMI group (P=0.028). The incidence of primary endpoint events in COPD with concurrent AMI group was higher than that in simple AMI group (27.0% vs 18.0%, P=0.002). The current study indicates that COPD patients with concurrent AMI have longer length of hospital stay and higher incidence of in-hospital events, which are worthy of significant attention in clinical practice.

Neurohormonal activation pattern in patients with atrial septal defect

Atrial septal defects (ASD) divert flow from systemic to pulmonary circulation, and some degree of plasma volume expansion and neurohormonal activation are necessary to maintain the effective circulatory volume. The aim of the present study was to understand the patterns of neurohormonal activation in ASD patients. 16 ASD patients and 10 controls were enrolled. Fasting blood samples were collected prior to procedure and 48 h after defect closure. At baseline, renin (185.0(79.0—437.0 vs. 79.4(60.8—110.0), p = 0.04), aldosterone (20.2 ± 7.6 vs. 11.7 ± 2.8, p < 0.001), copeptin (43.6 ± 27.5 vs. 16.4 ± 8.7, p = 0.002) and both natriuretic peptides were higher in ASD patients, while noradrenaline (113.0 ± 61.3 vs. 178.0 ± 49.4, p = 0.009) and endothelin-1 (2.93 ± 2.00 vs. 5.06 ± 1.25, p = 0.006) were higher in controls. After ASD closure, only NT-proBNP reduced significantly (p = 0.02). There were negative correlations between defect area with noradrenaline (r=-0.73, p = 0.002) and with endothelin-1 (r=-0.59, p = 0.02). Present findings suggest that in patients with an ASD, there is an increase in neurohormones that are related to regulation of plasma volume (aldosterone and arginine vasopressin) with simultaneous reductions in neurohormones related to vasoconstriction in systemic and pulmonary beds (noradrenaline and endothelin-1).

Diuretic efficiency of a single dose of subcutaneous versus oral furosemide after heart failure hospitalization across diuretic resistance strata: A pilot randomized controlled trial

AimsDiuretic resistance (DR) in heart failure (HF) is associated with worse outcomes. Furoscix®, a self‐administered subcutaneous (sc) furosemide injection administered via on‐body infusor, is approved for HF congestion relief. However, its efficacy in patients with DR post‐HF hospitalization remains unknown.Methods and resultsIn this open‐label pilot randomized controlled trial, 70 participants were randomized within 14 days post‐HF hospitalization to receive a single dose of 80 mg sc furosemide or home oral dose furosemide. Enrolment was stratified by presence of DR (admission BAN‐ADHF score ≥12) with a 2:1 enrolment of those with versus without DR. Key outcomes included diuretic efficiency, the total urine output per mg of diuretic administered, and peak urine sodium within 8 h of dose administration. Treatment effects were calculated as the difference in estimated marginal means across study groups and DR strata using linear mixed‐effect models. Overall, 70 participants were enrolled (57 years, 27% female, 70% Black, 79% with HF with reduced ejection fraction). Participants with DR (n = 46) had worse kidney function, higher N‐terminal pro‐B‐type natriuretic peptide, and higher home diuretic dose. Among participants with DR, sc furosemide versus oral furosemide led to significantly greater diuretic efficiency (34.0 vs. 22.6 ml/mg, p = 0.002) and peak urine sodium (100 vs. 83 mmol/L, p = 0.029), while participants without DR had similar diuretic efficiency (29.8 vs. 30.1 ml/mg, p = 0.94) and peak urine sodium (96 vs. 95 mmol/L, p = 0.93) across both treatments. DR significantly modified the effect of sc versus oral furosemide on diuretic efficiency (pinteraction: treatment × diuretic resistance = 0.022).ConclusionSingle‐dose sc furosemide was associated with greater diuretic efficiency and peak urine sodium than oral furosemide in participants with DR discharged following recent HF hospitalization.

Evaluation of Pentraxin-3 levels in children with multisystem inflammatory syndrome.

Early recognition of cardiac involvement and prediction of disease prognosis are essential for the management of inflammatory diseases such as multisystem inflammatory syndrome. This study aimed to investigate the role of Pentraxin-3 levels in identifying cardiac involvement and evaluating disease severity in patients with multisystem inflammatory syndrome. The study included 56 multisystem inflammatory syndrome patients and 26 healthy children as a control group. The multisystem inflammatory syndrome group was divided into those with cardiac involvement (n = 34) and those without (n = 22), as well as those with clinically mild-moderate (n = 30) and severe (n = 26) multisystem inflammatory syndrome. Blood samples for measurement of Pentraxin-3 levels were obtained from all patients before treatment and from the healthy controls. In the patient group, the mean age was 8.2 ± 4 years (range: 2-17 years), and the male-to-female ratio was 1.8. In the control group, these values were 9.5 ± 3.7 years (range: 2-16 years) and 1.9, respectively (p > 0.05). Plasma Pentraxin-3 levels were significantly higher in multisystem inflammatory syndrome patients compared to controls (7.1 ± 5 ng/mL vs. 2.9 ± 2.1 ng/mL, p = 0.001). Patients with cardiac involvement had a significantly higher median Pentraxin-3 level than those without (5.8 ng/mL vs. 4.1 ng/mL, p = 0.004). Severe disease was also associated with a higher median Pentraxin-3 level compared to mild-moderate disease (6.1 ng/mL vs. 4.4 ng/mL, p = 0.001). Pentraxin-3 level was negatively correlated with left ventricular ejection fraction and positively correlated with B-type natriuretic peptide, troponin. Elevated Pentraxin-3 levels in multisystem inflammatory syndrome patients may help predict the clinical course of the disease and cardiac involvement. However, larger-scale prospective studies are needed to further elucidate this.

Deletion of AT1a receptors selectively in the proximal tubules of the kidney alters the hypotensive and natriuretic response to atrial natriuretic peptide via NPRA/cGMP/NO signaling.

In the proximal tubules of the kidney, angiotensin II (ANG II) binds and activates ANG II type 1 (AT1a) receptors to stimulate proximal tubule Na+ reabsorption, whereas atrial natriuretic peptide (ANP) binds and activates natriuretic peptide receptors (NPRA) to inhibit ANG II-induced proximal tubule Na+ reabsorption. These two vasoactive systems play important counteracting roles to control Na+ reabsorption in the proximal tubules and help maintain blood pressure homeostasis. However, how AT1a and NPRA receptors interact in the proximal tubules and whether natriuretic effects of NPRA receptor activation by ANP may be potentiated by deletion of AT1 (AT1a) receptors selectively in the proximal tubules have not been studied previously. The present study used a novel mouse model with proximal tubule-specific knockout of AT1a receptors, PT-Agtr1a-/-, to test the hypothesis that deletion of AT1a receptors selectively in the proximal tubules augments the hypotensive and natriuretic responses to ANP. Basal blood pressure was about 16 ± 3 mmHg lower (P < 0.01), fractional proximal tubule Na+ reabsorption was significantly lower (P < 0.05), whereas 24-h urinary Na+ excretion was significantly higher, in PT-Agtr1a-/- mice than in wild-type mice (P < 0.01). Infusion of ANP via osmotic minipump for 2 wk (0.5 mg/kg/day ip) further significantly decreased blood pressure and increased the natriuretic response in PT-Agtr1a-/- mice by inhibiting proximal tubule Na+ reabsorption compared with wild-type mice (P < 0.01). These augmented hypotensive and natriuretic responses to ANP in PT-Agtr1a-/- mice were associated with increased plasma and kidney cGMP levels (P < 0.01), kidney cortical NPRA and NPRC mRNA expression (P < 0.05), endothelial nitric oxide (NO) synthase (eNOS) and phosphorylated eNOS proteins (P < 0.01), and urinary NO excretion (P < 0.01). Taken together, the results of the present study provide further evidence for important physiological roles of intratubular ANG II/AT1a and ANP/NPRA signaling pathways in the proximal tubules to regulate proximal tubule Na+ reabsorption and maintain blood pressure homeostasis.NEW & NOTEWORTHY This study used a mutant mouse model with proximal tubule-selective deletion of angiotensin II (ANG II) type 1 (AT1a) receptors to study, for the first time, important interactions between ANG II/AT1 (AT1a) receptor/Na+/H+ exchanger 3 and atrial natriuretic peptide (ANP)/natriuretic peptide receptor (NPRA)/cGMP/nitric oxide signaling pathways in the proximal tubules. The results of the present study provide further evidence for important physiological roles of proximal tubule ANG II/AT1a and ANP/NPRA signaling pathways in the regulation of proximal tubule Na+ reabsorption and blood pressure homeostasis.

Efficacy and Safety of Sotatercept Across Ranges of Cardiac Index in Patients with Pulmonary Arterial Hypertension: A Pooled Analysis of PULSAR and STELLAR

BackgroundThis analysis compared effects of the activin signaling inhibitor, sotatercept, across pulmonary arterial hypertension (PAH) subgroups stratified by baseline cardiac index (CI). MethodsPooled data from PULSAR (N=106; NCT03496207) and STELLAR (N=323; NCT04576988) were analyzed using two different CI thresholds, < and ≥ 2.0 L/min/m2 or 2.5 L/min/m2. Median differences in change from baseline at week 24 were evaluated using Hodges-Lehmann (HL) estimator and mean differences by least squares (LS), with 95% confidence intervals and p-values; p=0.05 was significant. Categorial endpoints and time-to-clinical worsening were analyzed by Cochran-Mantel-Haenszel and Cox model (hazard ratio (HR), respectively, without multiplicity adjustment. ResultsOf 429 participants, 51 and 378 had CI <2.0 L/min/m2 and ≥ 2.0 L/min/m2, respectively, whereas 179 and 250 had CI <2.5 L/min/m2 and ≥ 2.5 L/min/m2, respectively. Across all CI subgroups, sotatercept vs placebo significantly improved median 6-minute walk distance (range: 33.9 to 63.7 m: p<0.001), pulmonary vascular resistance (range: -202.8 to -395.4 dyn•s•cm-5; p≤0.002), and N-terminal pro-B-type natriuretic peptide (range: -317.3 to -1041.2 pg/mL; p<0.001). LS means showed reductions in pulmonary and right atrial pressures, decreased right ventricular size and enhanced tricuspid annular plane systolic excursion/ systolic pulmonary artery pressure in all subgroups. Sotatercept significantly delayed time to first occurrence of death or a worsening event in the subset of participants with CI ≥2.5 (HR 0.12; p<0.001), ≥2.0 (HR 0.13; p<0.001), and <2.5 (HR 0.21; p<0.001) L/min/m2. Improvements in World Health Organization functional class (all p<0.050) and European Society of Cardiology/European Respiratory Society risk score (all p<0.001) were seen within each subgroup. ConclusionsEfficacy and safety were consistent across baseline CI subgroups, supporting use of sotatercept in PAH patients irrespective of baseline cardiac hemodynamics.

Short-term impact of kampo goreisan in patients with congestive heart failure refractory to tolvaptan-incorporated medical therapy.

We often encounter patients with congestive heart failure refractory to conventional diuretics therapy. Kampo goreisan (Tsumura &Co. Tokyo, Japan) is receiving great concern in mediating body water balance, particularly for such a cohort. However, its detailed biological mechanism remains uncertain. Patients who received goreisan to treat congestive heart failure refractory to tolvaptan-incorporated medical therapy were prospectively included and observed for one week during the therapeutic period. The change in urine biomarkers during the first 24h was assessed as a primary concern. Baseline factors associated with an increase in urine volume during the first 24h were investigated as a secondary concern. A total of 18 patients were included. Median age was 81 (77, 86) and 12 (67%) were men. During the first 24h after the initiation of goreisan, urine cyclic AMP tended to decrease, urine aquaporin-2 decreased significantly, urine osmolality decreased significantly, and urine volume tended to increase. Baseline higher common logarithm of plasma B-type natriuretic peptide was associated with any increases in urine volume during the first 24h with an odds ratio of 73.2 (95% confidence interval 1.04-5149, p = 0.048). Baseline plasma B-type natriuretic peptide level had a positive correlation with a change in urine volume between baseline and day 1 (r = 0.533, p = 0.026). Goreisan may increase urine volume even in patients with congestive heart failure refractory to tolvaptan-incorporated medical therapy by modulating aquaporin-2 systems in the collecting duct, particularly in individuals with advanced heart failure accompanying significant congestion. Goreisan may have a regulatory effect on body fluid, rather than just forcing aquaresis.

Effect of optimisation to contemporary HFrEF medical therapy with sacubitril/valsartan (Entresto) and dapaglifloziN on left Ventricular reverse remodelling as demonstrated by cardiac magnetic resonance (CMR) Imaging: the ENVI study

IntroductionHeart failure with reduced ejection fraction (HFrEF) guidelines recommend ‘four pillars’ of medical therapy and device therapy if left ventricular ejection fraction (LVEF) remains ≤35% after 3 months optimum medical...

Prevalence of Neurogenic Stress Cardiomyopathy in Acute Ischemic Stroke and Relationship with Leukocytosis

Describe the prevalence and features of neurogenic stress cardiomyopathy in acute ischemic stroke. Describe leukocytosis as an inflammatory marker in neurogenic stress cardiomyopathy. Retrospective review of 688 adult ischemic stroke patients at a tertiary care center (1/2018 - 12/2021). Neurogenic stress cardiomyopathy was identified by one of: low left ventricular ejection fraction, ventricular wall motion abnormalities, elevated Troponin-I, or elevated brain natriuretic peptide. Leukocytosis defined as white blood cell count ≥12.0 × 10^9/L. Clinical and demographic data were collected. Neurogenic stress cardiomyopathy was observed in 147 (21%) patients. In this group, mean age was 68, 44% were female, mean National Institutes of Health Stroke Scale was 10 and mean hospital stay was 8 days. Low left ventricular ejection fraction (median 40%) was observed in 64% of these patients, elevated Troponin-I (median 0.252 ng/mL) in 40%, and ventricular wall motion abnormalities in 55%. Stroke mechanisms were cryptogenic (43%), cardioembolic (24%), small vessel disease (13%), large artery atherosclerosis (12%), and other (8%). Mean white blood cell count was 8.63 × 10^9/L. Leukocytosis occurred in 12% of patients with cardiomyopathy and 8% without, with no significant difference (p=0.9). We propose defining neurogenic stress cardiomyopathy by one of four cardiac biomarkers. The prevalence aligns with prior reports, most frequently identified by low left ventricular ejection fraction or ventricular wall motion abnormalities. Unlike Takotsubo Cardiomyopathy, abnormal wall motion patterns were predominantly diffuse. No significant difference in leukocytosis was found between groups. Further research is needed to identify neurogenic stress cardiomyopathy risk factors.

Relationship of Iron Deficiency, Anemia and Combination of Iron Deficiency With Anemia With Severity of Manifestations of Chronic Heart Failure. Additional Analysis of the Study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (J-CHF-RF)".

Aim To evaluate the role of iron deficiency (ID) identified by various criteria, anemia, and the combination of ID and anemia in determining the severity of the clinical course of chronic heart failure (CHF) in a retrospective analysis of data from 498 patients who participated in the ID-CHF-RF Russian multicenter program.Material and methods ID was diagnosed by the following three criteria established by the European Society of Cardiology (ESC) and the Russian Society of Cardiology (RSC): 1) ferritin concentration &lt;100 μg/l or ferritin concentration 100-299 μg/l in combination with a decreased transferrin saturation (TS) &lt;20%; 2) ID criteria that showed a high sensitivity and specificity when compared with bone marrow morphology (BMM): TS ≤19.8% or serum iron (SI) ≤13 μmol/l; and 3) a composite index including a ferritin concentration &lt;100 μg/l in combination with TS &lt;20% and SI ≤13 μmol/l. The presence of anemia was defined as a hemoglobin concentration of less than 12.0 g/dl in women and less than 13.0 g/dl in men according to the criteria of the World Health Organization.Results Concomitant anemia was detected in 40.3% of patients with CHF; in 85.1% of cases, anemia was combined with the SI concentration below normal. CHF patients with concomitant anemia were significantly older and had low levels of not only red blood cells and hemoglobin but also all parameters of iron metabolism, i.e., SI, ferritin concentration, and TS. The mean deviation of the red blood cell size, that characterizes the degree of anisocytosis, was significantly increased in patients with anemia, especially with a low SI. These patients had a higher CHF functional class, elevated levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) and walked a shorter distance in the 6-minute walk test, which reflects significantly more severe manifestations of CHF with concomitant anemia, particularly in combination with a low SI. The incidence of ID was 83.1% (including 23.3% in combination with anemia) according to the ESC/RSC criteria; 74.5% (including 43.3% with anemia) according to the BMM criteria; and 51.6% (including 51.7% with anemia) according to the composite index, which seems to be stricter compared to the first two criteria. Regardless of the assessment method (by total weighted average data), in ID combined with anemia, not only the hemoglobin concentration was significantly reduced but all three analyzed parameters of iron metabolism were also significantly reduced (SI 9.0 μmol/l vs. 10.4 μmol/l; ferritin 41 μg/l vs. 59 μg/l; TS 8.5% vs. 12.9%) compared to ID without anemia, respectively. The CHF severity and the NT-proBNP concentration were also maximum for the combination of ID and anemia, in contrast to ID without anemia, regardless of the ID criterion used. A more accurate comparison of the methods for determining ID in CHF in the context of their prognostic value will be obtained by analyzing the data of a two-year follow-up of patients in this study, which will be the subject of the next article.Conclusion This analysis suggests that the presence of concomitant ID without anemia or anemia without ID moderately affects the severity of clinical manifestations of CHF and may be rather markers than factors determining the course of the disease, and in this case, does not require special correction with iron medications. And only ID anemia (a combination of ID with anemia) in patients with CHF can be considered a condition requiring special correction (for example, with intravenous medication) in addition to optimal therapy for CHF. This conclusion does not change depending on the used criteria for ID and requires verification in new RCTs.

Features of indicators of macrohemodynamics and systemic inflammation in patients with community-acquired pneumonia combined with gastroesophageal reflux disease

Relevance. The clinical course, treatment approaches, and outcomes of community-acquired pneumonia (CAP) often depend on microcirculatory disorders. The significant prevalence of gastroesophageal reflux disease (GERD) in the population determines the frequency of CAP. Study of the pathogenetic basis of the combined course of CAP in individuals with GERD, incl. microcirculation systems, can target correction paths and increase the effectiveness of therapy.Objective. To identify indicators of systemic inflammation and macrohemodynamics in patients with CAP combined with GERD.Material and methods. A total of 123 patients were under observation, incl. with mild CAP without signs of GERD (group I) — 38, with CAP and GERD — 49 (group 2), and 36 patients with GERD without CAP — group 3. In all patients with CAP, along with traditional studies, the concentrations of C-reactive protein (CRP) and brain natriuretic peptide (BNP) were determined in the blood, and echocardioscopy (EchoCS) was performed to determine the end systolic (ES) and diastolic (ED) volumes of the left ventricle (LV) and right ventricles (RV), blood flow velocity at the level of the pulmonary artery (Vmax PA), pressure gradients ΔPmax at the level of the tricuspid valve (TV), PA, and LV isovolumic relaxation time (IVRT). Control values for indicators were obtained from 34 practically healthy donors.Results. In all patients with CAP, at the beginning of therapy, intoxication and respiratory syndromes were observed, and pneumonia was diagnosed on an X-ray. Patients in groups II and III had characteristic symptoms of GERD. Blood tests revealed leukocytosis in all patients with CAP. The initial CRP concentration in group 1 was 5.2, group 2 — 7.7, group 3 — 1.2 times higher than normal. The initial concentration of BNP in all groups did not differ from the control. By discharge, CRP levels in all patients had decreased: however, in group II, they remained higher than in healthy people (2.6 times (p &lt; 0.05) and higher than in group I, 1.3 times (p &lt; 0.05). Before discharge, the BNP level in group II increased by 1.2 times compared with baseline in group I, in healthy individuals, and in group III. When analyzing the EchoCS indicators in group II patients, a significant increase in the initial indicators of LV EDV and LV ESV and decrease in EF and IVRT were observed. After treatment, no significant dynamics of volume and velocity parameters were observed in patients in group II; in patients in group I, pressure gradients at the TC and PA levels remained slightly reduced.Conclusions. An increase in CRP levels in patients with GERD characterizes low-intensity inflammation, which potentiates systemic inflammation in patients with CAP combined with GERD and is accompanied by an increase in BNP.