Plasma B-type Natriuretic Peptide Research Articles

Electrochemical Determination of B-Type Natriuretic Peptide with an Epitope-Imprinted Polymer-Based Sensor

B-type natriuretic peptides (BNP) are produced and secreted by the myocardium to reduce blood pressure and cardiac load. They cause vasodilation, natriuresis, growth suppression, and inhibition of the sympathetic nervous system and the renin–angiotensin–aldosterone system. The measurement of plasma BNP levels provides clinically useful information concerning the diagnosis and management of left ventricular dysfunction and heart failure, complementing other diagnostic testing procedures. In this work, three epitopes from the N-terminal (BNPnt), C-terminal (BNPct), and the cystine-bridged cyclic peptides (BNPr) of B-type natriuretic peptides were synthesized as templates for molecular imprinting. These peptides were doped into aniline (AN) and m-aminobenzenesulfonic acid (MSAN) for electropolymerization, thus forming epitope-imprinted poly(AN-co-MSAN) conductive films (EIPs). The monomer ratio was optimized using the electrochemical signals during polymerization. The optimized films were then characterized using a scanning electron microscope (SEM), atomic force microscope (AFM), and AC impedance. The electrochemical response of the films to the target peptides and to BNP was then measured. The sensing range of the EIPs-coated electrodes was from 0.001 to 1000 pg/mL for BNP. Finally, the BNP concentration in diluted serum samples was measured with the BNPrIP-coated electrode, giving 3.15 ± 0.07 pg/mL. By spiking the sample with known BNP concentrations, the accuracy was determined to be better than ±5%.

Association between impaired left ventricular global longitudinal strain and B-type natriuretic peptide in obstructive hypertrophic cardiomyopathy

Abstract Background Left ventricular global longitudinal strain (LV-GLS) is considered valuable in explaining impaired left ventricular contractility in hypertrophic cardiomyopathy (HCM) with preserved ejection fraction and is associated with worse outcome. Elevated B-type natriuretic peptide (BNP) is a biomarker of increased LV wall stretch and a risk factor of heart failure, mortality, and other adverse cardiovascular events. However, relationship between GLS and BNP has not received sufficient attention in the obstructive variant of HCM. Purpose This study aimed to determine the association between echocardiographic LV-GLS and plasma BNP in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods A total of 145 consecutive patients (32% females) with symptomatic HOCM were enrolled in the retrospective study. HOCM was defined with a maximum end-diastolic wall thickness ≥15mm without other etiologies for LV hypertrophy, and peak LV outflow tract (LVOT) gradient ≥30mmHg. The echocardiographic parameters regarding LV geometry, loading conditions, and GLS were evaluated according to guidelines. Patients were divided into two groups according to absolute GLS values (greater or lower than median LV-GLS). Patient baseline clinical data, echocardiographic parameters, and BNP were compared. Univariate and multivariable regression analysis were applied to identify the independent determinator of LV-GLS. Results The median value of LV-GLS of this study cohort was -13.4%. Eighty-one patients (47.6±13.4 years-old) had a |GLS|≥13.4% and 64 individuals (48.7±12.6 years-old) had a |GLS|<13.4%. No differences were found in age, gender, physical examinations, LVEF, cardiovascular comorbidities, or active medications between the two groups, except for body mass index (BMI). Patients with |GLS|≥13.4% had statistically lower BMI (24.58±2.42 vs. 26.00±3.12kg/m², p=0.030). BNP was found significantly elevated in patients with |GLS|<13.4% when compared with individuals with |GLS|≥13.4% {median (IQR); 550.05 (214.50, 899.35) vs. 182.40 (78.90, 479.90)pg/mL, p=0.004}. In univariate regression analysis, decreased |GLS| was associated with male gender, maximum and mean LV wall thickness, peak LVOT gradient, reduced mitral annular e’ velocity, elevated BNP and cardiac troponin I. In multivariable regression analysis, GLS was found independently associated with mean LV wall thickness and BNP. Conclusions In patients with symptomatic HOCM with preserved ejection fraction, impaired LV-GLS was found to be associated with plasma BNP and mean LV wall thickness, independent of gender, age, loading conditions, LVEF, or LVOT gradient. Reduced GLS may be a more sensitive surrogate in assessing increased myocardial wall tension or stretch, rather than LV contractility in these patients. Therefore, the interpretation of GLS in HOCM should shift away from systolic interest toward emphasizing its potential value in risk stratification of diastolic heart failure with preserved LVEF.Figure 1

Serum transferrin concentration: a new prognostic biomarker in heart failure with reduced ejection fraction

Abstract Introduction Iron deficiency (ID) is a common comorbidity in patients with reduced heart failure (HFrEF), and is associated with poor clinical status and outcomes, but there is not enough data investigating serum transferrin concentration (STC) as a biomarker HFrEF to predict prognosis and mortality. Purpose We investigated relationship between STC at admission and all-cause mortality during follow-up in HFrEF. Methods We reviewed the medical data of 420 patients hospitalised in our institution for HFrEF over a period of 18 months. Laboratory tests were performed on the first 24 hours of admission. Patients were divided into two groups according to STC, using the value of 199 μg/dl as the cut-off. This value was determined from the ROC analysis to be the value with the highest sensitivity and specificity. Then we analysed relationship between STC at admission and all-cause mortality during follow-up between the two groups, after adjustment of the various variables described in the literature. Results Of 420 patients with HFrEF, 18.6% had STC ≤ 199 μg/dl (group 1) and 81.4% had STC > 199 μg/dl (group 2) with no difference in age and sex distribution (p = 0.873 ; p = 0.304). Patients with low STC were more likely to be diabetic (70.5% vs 46.5% ; p < 0.001), have dyslipidemia (52.6% vs 33%; p = 0.002), and history of chronic renal failure (6.4% vs 2.0% ; p = 0.045). There was no relation between STC and NYHA class (p = 0.776), hospital stay (p = 0.491) nor EF (p = 0.146). Biologically, lower STC was significantly associated with higher serum ferritin (292.77 vs 198.17 ; p < 0.001), TSAT (68.30 vs 22.21 ; p = 0.020) and C-reactive protein (CRP) (124.91 vs 39.98 ; p = < 0.001), lower plasma B-type natriuretic peptide (BNP) (5798.32 vs 6449.97 ; p = 0.002), with no difference in haemoglobin level (p = 0.272) and estimated glomerular filtration rate (eGFR) (p = 0.260). The prevalence of iron deficiency by the ESC criteria was lower in those with low STC; ferritin < 100 μg/l (15.4% vs 29.2% ; p = 0.015) or TSAT < 20% (33.3% vs 51,8% ; p = 0.004). There was no difference between the two groups in term of NYHA class and EF at three months (p = 0.87, p = 0.108). However, all-cause mortality during follow-up was significantly associated with low STC (37.2% vs 17.0% ; p <0.001). (Figure 1) In multivariable analysis, all-cause mortality was independently associated with STC ≤ 199 μg/dl (HR 1.71; 95% CI : 1.08 ; 2.7 ; p = 0.02). This is the same finding for the ischaemic origin of HFrEF (HR 2.1 ; p = 0.001), therapeutic inertia during follow-up (HR 5.53 ; p <0.001) and EF < 36% (HR 1.03 ; p = 0.047) (Figure 2). Conclusion More data are required before the routine use of STC as a biomarker of prognosis in HFrEF, but it may represent a reliable and cost-effective option to predict mortality.FIGURE 1FIGURE 2

Impact of Remote Dielectric Sensing on Predicting Worsening Heart Failure During Hospitalization for Heart Failure.

Background: A remote dielectric sensing (ReDS) system quickly quantifies pulmonary congestion. Nonetheless, its efficacy in predicting an in-hospital increase in plasma B-type natriuretic peptide levels, the potential surrogate of worsening heart failure, remains undetermined. Methods: Patients who underwent ReDS measurement on admission during their hospitalization in the general wards for heart failure between 2021 and 2022 were eligible. The impact of the baseline ReDS value, completely blinded to the attending clinicians, on the in-hospital increase in plasma B-type natriuretic peptide levels of >100 pg/mL from index admission was evaluated. Results: A total of 147 patients admitted with acute-on-chronic heart failure (median age: 79 years; 76 men) were included. The median ReDS value on admission was 28% (25%, 34%). Eighteen patients experienced the primary outcome: plasma B-type natriuretic peptide levels increasing from 461 (207, 790) pg/mL (baseline) to 958 (584, 1290) pg/mL (maximum) (p < 0.001). The ReDS value on admission was an independent predictor of the primary outcome, with an adjusted odds ratio of 1.07 (95% confidence interval: 1.01-1.14; p = 0.028) with an optimal cutoff of 32%. Conclusions: The ReDS system could be a promising tool for predicting in-hospital worsening heart failure in patients hospitalized for heart failure when measured upon admission. The clinical implication of ReDS-guided management of heart failure during index hospitalization requires further studies.

Correlations Between Plasma BNP Level and Risk of Thrombotic-Hemorrhagic Events After Left Atrial Appendage Closure.

Background: Percutaneous left atrial appendage closure (LAAC) reduces the incidence of stroke/bleeding events in patients with non-valvular atrial fibrillation, high risk of stroke, and contraindication in continuing anticoagulation therapy. Of them, patients with heart failure may remain at high risk of these events after LAAC. Method: Patients who underwent LAAC and were listed for the multi-center, prospectively collected OCEAN-LAAC registry, were eligible. Of them, individuals without baseline plasma B-type natriuretic peptide (BNP) levels and those dependent on hemodialysis were excluded. The prognostic impact of baseline plasma BNP levels on the incidence of death or stroke/bleeding events after LAAC was evaluated. Results: A total of 937 patients (median 78 years, 596 men) were included. The LAAC device was successfully implanted in 934 (98%) patients. Over the 366 (251, 436) days after the LAAC, 148 patients encountered a primary outcome. The common logarithm of baseline plasma BNP was independently associated with the primary outcome with an adjusted hazard ratio of 1.46 (95% confidence interval 1.06-2.18, p = 0.043). A calculated cutoff of 2.12 (equivalent to 133 pg/mL of plasma BNP level) significantly stratified the cumulative incidence of the primary outcome (29% vs. 21% for 2 years, p = 0.004). Conclusions: Using prospectively collected large-scale multi-center Japanese registry data, we demonstrated that a baseline higher plasma BNP level was independently associated with a higher incidence of stroke/bleeding events and mortality after LAAC. Further studies are warranted to understand the optimal therapeutic strategy for LAAC candidates with elevated baseline plasma BNP levels.

Catestatin as a predictor for cardiac death in heart failure with mildly reduced and preserved ejection fraction.

Endogenous catecholamine release-inhibitory peptide catestatin has been associated with heart failure (HF). This subgroup analysis of our cohort of HF compared the different effects of catestatin as a predictor for cardiac outcomes in patients with HF with reduced (HFrEF), mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction. Plasma catestatin was measured in the HF patient cohort of 228 cases with a whole spectrum of ejection fraction. The cardiac deaths were analysed according to prespecified subgroups. Over a median follow-up of 52.5months, the association between plasma catestatin and cardiac death was different in patients with HFrEF, HFmrEF or HFpEF [hazard ratio (HR) 1.53, 95% confidence interval (CI) 0.99-2.37 and HR 2.73, 95% CI 1.56-4.75, respectively; interaction P=0.022]. Patients with HFmrEF/HFpEF were older and more likely to be female, with non-ischaemic cardiomyopathy and atrial fibrillation but lower levels of plasma B-type natriuretic peptide (BNP). Similar adverse cardiac events occurred in patients with HFmrEF/HFpEF as in HFrEF. Plasma catestatin was a better predictor for cardiovascular death in the HFmrEF/HFpEF patients [area under the receiver operating characteristic curve (AUC)=0.72, 95% CI 0.45-0.74] than in the HFrEF patients (AUC=0.59, 95% CI 0.587-0.849). The optimal cut point of plasma catestatin level of 0.86ng/mL predicted a 2.80-fold elevated risk for cardiac death in HFmrEF/HFpEF. Elevated plasma catestatin might be a more sensitive predictor for cardiac outcome in patients with HFmrEF/HFpEF than in HFrEF.

Comparison of Plasma B-type Natriuretic Peptide (BNP) Levels, N-terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels, and the NT-proBNP-to-BNP Ratio in Patients with CKD

Comparison of Plasma B-type Natriuretic Peptide (BNP) Levels, N-terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels, and the NT-proBNP-to-BNP Ratio in Patients with CKD

Effects of Dapagliflozin in Combination with Hydrochlorothiazide on Cardiac Remodeling in Rats with Heart Failure After Myocardial Infarction.

In addition to its antihypertensive and diuretic effects, hydrochlorothiazide also demonstrates additional cardioprotective properties; however, the existence of a synergistic interaction between dapagliflozin and hydrochlorothiazide remains unclear.To establish a rat model of heart failure for investigating the effects and mechanisms of dapagliflozin in combination with hydrochlorothiazide during early intervention, H9c2 cells were cultured to validate their in vitro efficacy. The combination group exhibits a synergistic improvement in hemodynamics, ejection fraction, and a reduction in plasma B-type natriuretic peptide concentration. This combination effectively decreases collagen volume fraction and the expression of collagen I and III, p47phox, p67phox, NF-κB p65, Bax, and caspase-3. The combination group demonstrates a synergistic effect in enhancing cardiac function, attenuating oxidative stress and inflammation. The in vitro effects of the combination were demonstrated in H9c2 cardiomyocytes. In addition, the combination exhibits a more pronounced inhibitory effect on NHE1 expression. The expression of NHE1 in H9c2 cells is inhibited by hydrochlorothiazide, thereby alleviating the consequences of NHE1 overexpression. The results of molecular docking and kinetic simulations indicate a strong binding affinity (-6.1 kcal/mol) between hydrochlorothiazide and NHE1, resulting in the formation of a stable conformation. This may elucidate the underlying mechanism responsible for the synergistic effects of drugs.The combination of dapagliflozin and hydrochlorothiazide has synergistic effects on improving cardiac function, oxidative stress, and inflammation in rats with heart failure. Hydrochlorothiazide binds to and inhibits the expression of NHE1, thereby enhancing dapagliflozin's inhibitory effect on NHE activity. This mechanism potentially elucidates its enhanced cardioprotective effects.

Sigmoidal heart rate response pattern during exercise in patients with chronic heart failure.

Detailed heart rate (HR) response patterns during exercise in patients with heart failure (HF) and sinus rhythm remain uncertain. We screened consecutive patients with HF who underwent cardiopulmonary exercise tests at a large academic center from November 2013 to July 2023. HR response during exercise was statistically classified using logistic differential equation models. A total of 99 patients were included. Of them, 75 patients were assigned to "sigmoidal pattern" and the other 24 to "exponential pattern." Patients with the sigmoidal pattern were older and exhibited higher plasma B-type natriuretic peptide levels. Increases in HR and oxygen consumption (V̇o2)/kg up to the anaerobic threshold level were not different between both patterns. However, beyond the threshold, the sigmoidal pattern group showed no further increase in HR and significantly lower V̇o2/kg than their counterparts (interactions for P < 0.001). HR response during exercise in patients with heart failure and sinus rhythm was categorized into two unique groups: sigmoidal and exponential patterns. More detailed clarification of the sigmoidal pattern, potentially indicating sinus node dysfunction, should offer new clinical insights for chronotropic incompetence.NEW & NOTEWORTHY Heart rate response patterns can be classified into two groups among patients with chronic heart failure reaching maximal exertion: sigmoidal and exponential.

Efficacy and safety of the urate-lowering agent febuxostat in chronic heart failure patients with hyperuricemia: results from the LEAF-CHF study.

Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure (CHF). To determine whether febuxostat, a urate-lowering agent, may improve clinical outcomes in CHF patients, we conducted a multicenter, prospective, randomized, open-label, blinded endpoint study with a treatment period of 24weeks. We randomly assigned Japanese outpatients diagnosed with both CHF with reduced left ventricular ejection fraction (LVEF < 40%) and asymptomatic hyperuricemia (serum uric acid [UA] levels > 7.0mg/dl and < 10.0mg/dl) to either a febuxostat group (n = 51) or a control group (n = 50). The primary efficacy endpoint was the change in log-transformed plasma B-type natriuretic peptide (BNP) levels from baseline to week 24 (or at discontinuation). The secondary efficacy endpoints were the changes in LV systolic or diastolic function evaluated by echocardiography, New York Heart Association (NYHA) class, hemoglobin, and estimated glomerular filtration rate from baseline to week 24, and the change in log-transformed plasma BNP levels or serum UA levels from baseline to weeks 4, 8, 12, 16 and 20 (BNP) or weeks 4, 8, 12, 16, 20 and 24 (serum UA). The primary safety endpoints were occurrence of all-cause death or major cardiovascular events. The mean age of participants was 70years; 14% were female. The febuxostat group and the control group did not differ with respect to the primary efficacy endpoint (p = 0.13), although the decrease in log-transformed plasma BNP levels from baseline to each of weeks 4, 8, 12, 16 and 20 was greater in the febuxostat group. There were no significant differences between the two groups in the primary safety endpoints or the secondary efficacy endpoints except reduced serum UA levels in the febuxostat group. Febuxostat did not reduce plasma BNP levels at week 24 in patients with CHF, but it appeared safe with no increase in major cardiovascular events and all-cause or cardiovascular mortality.

Importance of fourth heart sound and preserved left atrial function in wild-type transthyretin amyloidosis.

A fourth heart sound (S4) was reported to be almost never present in patients with amyloid light-chain cardiomyopathy. There have been no reports on S4 in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). This study aimed to clarify the clinical implications of S4 in patients with ATTRwt-CM. Seventy-six patients with ATTRwt-CM (mean age: 80.4±5.4years, 68 males) who had undergone phonocardiography (PCG) were retrospectively assessed. We measured S4 amplitude on digitally recorded PCG. S4 was considered to be present when its amplitude was 1.0mm or greater on the PCG. Distinct S4 was defined as S4 with an amplitude of 2.0mm or greater, which is usually recognizable by auscultation. According to the rhythm and presence or absence of S4, the patients were divided into three groups, namely, sinus rhythm (SR) with S4, SR without S4, and non-SR. Non-SR consisted of atrial fibrillation, atrial flutter, and atrial tachycardia. Thirty-six patients were in SR and the remaining 40 patients were in non-SR. In the 36 patients in SR, S4 was shown by PCG to be present in 17 patients (47%), and distinct S4 was recognized in 7 patients (19%) by auscultation. In patients who were in SR, those with S4 had higher systolic blood pressure (124±15 vs. 99±8mmHg, P<0.001), lower level of plasma B-type natriuretic peptide (308 [interquartile range (IQR): 165, 354] vs. 508 [389, 765] pg/mL, P=0.034) and lower level of high-sensitivity cardiac troponin T (0.068 [0.046, 0.089] vs. 0.109 [0.063, 0.148] ng/mL, P=0.042) than those without S4. There was no significant difference in left atrium (LA) volume index or LA reservoir strain between patients with S4 and without S4. Patients with S4 had more preserved LA systolic function than those without S4 (peak atrial filling velocity: 53±25 vs. 34±9cm/s, P=0.033; LA contractile strain: 4.1±2.1 vs. 1.6±2.0%, P=0.012). Patients in SR without S4 had worse short-term prognosis compared with the other two groups (generalized Wilcoxon test, P=0.033). S4 was present in 47% of the patients in SR with ATTRwt-CM. Patients in SR without S4 had more impaired LA systolic function than those in SR with S4. The absence of S4 portends a poor short-term prognosis in patients with ATTRwt-CM.

Impaired Gastrointestinal Motility and Worsening Heart Failure in Patients Receiving Trans-Catheter Aortic Valve Replacement.

Background: Impaired gastric motility in the form of constipation may often occur in elderly patients with chronic heart failure. Candidates for trans-catheter aortic replacement (TAVR) are of old age and have multiple comorbidities, probably including constipation. However, the clinical implication of a history of constipation in patients receiving TAVR remains unknown. Methods: Patients who underwent TAVR at our large academic center between 2015 and 2022 were eligible. The prognostic impact of the prescribed laxative type and number, which was assumed as the severity of constipation, on the incidence of death or heart failure readmission two years after index discharge was investigated. Results: A total of 344 patients were included. Median age was 85 years, and 99 patients were men. Patients with any laxatives (N = 166) had higher systolic blood pressure, higher plasma B-type natriuretic peptide levels, and a lower prescription rate of renin-angiotensin system inhibitors at the time of index discharge after TAVR (p < 0.05 for all). The number of laxative types was independently associated with the composite primary outcome with an adjusted hazard ratio of 1.83 (95% confidence interval 1.27-2.63, p = 0.001) with a cutoff of one type of laxative used, which significantly stratified the 2-year cumulative incidence of the primary outcome (18% versus 7%, p = 0.001). Conclusions: The presence of constipation was associated with worse clinical outcomes following TAVR. The prognostic impact of an aggressive intervention for constipation remains a future concern in this cohort.

Plasma B-type natriuretic peptide is independently associated with cardiovascular events and mortality in patients with chronic kidney disease

The association between B-type natriuretic peptide (BNP) and cardiovascular (CV) events and mortality has not been well characterized in patients with chronic kidney disease (CKD). We prospectively investigated whether BNP was associated with CV events or mortality beyond cardiac alterations in 1078 patients with CKD. Participants were divided into the following 3 groups according to circulating BNP concentration: < 40 pg/mL, low; 40–100 pg/mL, middle; and > 100 pg/mL, high. Primary outcome was fatal or nonfatal CV events, and alternative outcome was a composite of fatal or nonfatal CV events, or non-CV deaths. During a median follow-up of 2.6 years, CV and composite events occurred in 158 and 248 participants, respectively. Cox analyses after adjustment for covariates, including cardiac parameters, showed that the hazard ratios (HRs) (95% confidence intervals [CIs]) for CV events of middle and high groups were 1.00 (0.63, 1.58) and 1.72 (1.06, 2.79), respectively, compared with low group. Additionally, similar results were obtained for composite events; the HRs (95% CIs) of middle and high groups were 1.10 (0.77, 1.57) and 1.54 (1.04, 2.27), respectively, compared with low group. Thus, in CKD, high BNP concentrations were independently associated with CV events and mortality, independent of cardiac alterations.

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.

Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R=-0.30, P<0.001) and fewer daily steps (R=-0.19, P=0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6months were positively related (R=0.25, P=0.004). This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

Increased Systemic Levels of Centrally Acting B-Type Natriuretic Peptide Are Associated with Chronic Itch of Different Types

B-type natriuretic peptide (BNP) is an itch-selective neuropeptide that was shown to play a role in both histaminergic and nonhistaminergic itch in mice. It was also shown that elevated serum BNP is linked to increased pruritus in nondiabetic hemodialysis patients. This study examined plasma BNP levels of 77 patients and N-terminal pro-BNP levels of 33 patients with differing types of chronic itch to see whether BNP and N-terminal pro-BNP levels can correlate with itch severity. Plasma BNP and N-terminal pro-BNP levels of all patients with itch correlated with itch numerical rating scale and in particular for patients with chronic pruritus of unknown origin. On the basis of this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by intravenous or osmotic pump induced significant scratching. In addition, pharmacological and ablation strategies determined that BNP acts centrally by activating the natriuretic peptide receptor A in the dorsal horn of the spinal cord. These data support that BNP and N-terminal pro-BNP levels are associated with chronic itch and may be used in clinical setting.

Predictive Factors of Cardiac Mortality Following TEER in Patients with Secondary Mitral Regurgitation

Background: Transcatheter edge-to-edge mitral valve repair (TEER) has emerged as a viable approach to addressing substantial secondary mitral regurgitation. In the contemporary landscape where ultimate heart failure-specific therapies, such as cardiac replacement modalities, are available, prognosticating a high-risk cohort susceptible to early cardiac mortality post-TEER is pivotal for formulating an effective therapeutic regimen. Methods: Our study encompassed individuals with secondary mitral regurgitation and chronic heart failure enlisted in the multi-center (Optimized CathEter vAlvular iNtervention (OCEAN)-Mitral registry. We conducted an assessment of baseline variables associated with cardiac death within one year following TEER. Results: Amongst the 1517 patients (median age: 78 years, 899 males), 101 experienced cardiac mortality during the 1-year observation period after undergoing TEER. Notably, a history of heart failure-related admissions within the preceding year, utilization of intravenous inotropes, and elevated plasma B-type natriuretic peptide levels emerged as independent prognosticators for the primary outcome (p &lt; 0.05 for all). Subsequently, we devised a novel risk-scoring system encompassing these variables, which significantly stratified the cumulative incidence of the 1-year primary outcome (16%, 8%, and 4%, p &lt; 0.001). Conclusions: Our study culminated in the development of a new risk-scoring system aimed at predicting 1-year cardiac mortality post-TEER.

Value of C-reactive protein/albumin ratio in predicting the development of preoperative oxygenation impairment in patients with Stanford type-B acute aortic dissection

ObjectivesWe aimed to assess the predicting value of C-reactive protein (CRP)/albumin ratio (CAR) in the development of Oxygenation impairment (OI) in the patients with Stanford type-B acute aortic dissection (AAD). MethodsThis study included 133 patients (age = 58.8 ± 12.0 years, median age = 61 years, Male/Female = 117/16) diagnosed as Stanford type-B AAD accompanied by hypertension from July 2012 to May 2020.Clinical data were retrospectively extracted from the database. The patients in this study were divided into OI group (oxygenation index ≤ 200) and non-OI group (oxygenation index > 200). Clinical characteristics in both groups were compared, and predicting value of CAR in the development of OI was assessed. ResultsPatients in OI group had higher peak body temperature (37.94 ± 0.62 vs. 37.67 ± 0.51 ℃, P =.010), higher levels of serum CRP (41.74 ± 27.71 vs 15.21 ± 19.66 mg/L, P =.000) and plasma B-type natriuretic peptide (292.14 ± 251.11 vs 179.80 ± 241.27 ng/L, P =.016), lower levels of albumin (34.00 ± 5.14 vs 37.72 ± 5.24 g/L, P =.000), and higher CAR (1.27 ± 0.89 vs 0.41 ± 0.53, P =.000). In multivariate regression analysis, CAR (odds ratio: 5.215, 95 % CI: 2.682; 10.137, P =.000) and the peak body temperature (odds ratio: 2.905, 95 % CI: 1.255; 6.724, P =.013) could significantly predict the OI development. The AUC for CAR was 0.831 (95 % CI: 0.756–0.907). An optimal cutoff value for CAR for predicting OI was ≥ 0.70, with a sensitivity of 67.5 % and a specificity of 88.2 %. ConclusionsCompared with CRP or albumin alone, the CAR might be a more accurate marker in predicting OI development in Stanford type-B AAD.

Left Atrial Stiffness Increases after Trans-Catheter Atrial Septal Closure.

Transcatheter atrial septal closures for secundum atrial septal defects (ASD) have demonstrated favorable clinical outcomes. However, the impact of device implantation on the stiffness of the left atrium remains unclear. Patients with secundum ASD undergoing transcatheter closure and follow-up right heart catheterization at six months were included. We investigated the relationship between post-procedural (E/e' ratio)/(LAs strain) ratio, an index of left atrial stiffness, and baseline characteristics, including echocardiographic and hemodynamic parameters. Forty patients were included (median 69 (56, 75) years, 12 men, and pulmonary systemic flow ratio 2.27 (1.96, 2.86)). Trans-catheter ASD closure was successfully performed without any major complications, accompanying a significant reduction in right ventricular to left ventricular size ratio from 1.04 (0.87, 1.13) to 0.74 (0.66, 0.86) (p < 0.01). The (E/e' ratio)/(LAs strain) ratio was markedly elevated the day after the procedure and was further increased 6 months later (before: 0.25 (0.17, 0.34), 1 day later: 0.34 (0.27, 0.50), 6 months later: 0.43 (0.27, 0.76), p < 0.01). The groups with higher (E/e' ratio)/(LAs strain) ratios at 6 months had significantly more severe heart failure conditions including lower cardiac output and higher plasma B-type natriuretic peptides. Patients undergoing transcatheter ASD closure experienced improvement in hemodynamics and clinical symptoms but an elevation in left atrial stiffness post-procedure. The clinical ramifications of this finding, particularly during the longer-term observation period subsequent to ASD closure, warrant further investigation.

Assessment of plasma B-type natriuretic peptide and highly sensitive C- reactive protein among diagnosed patients of diabetes mellitus with and without cardiovascular disease

Background: Considering the burden of cardiovascular disease (CVD) complications in patients with diabetes and the production of BNP on the incidence of CVD. Aims and Objectives: We investigated the role of BNP and high sensitive C-reactive protein (hs-CRP) in predicting the presence of CVD in diabetes and determined if the concentration load of BNP and hs-CRP differed in diabetics participants with CVD and without CVD. Materials and Methods: Diabetic consenting participants fitting the study inclusion criteria were enrolled. Based on medical records, participants were grouped into diabetes with CVD and diabetes without CVD and tested for blood BNP, hs-CRP, Lipid Profile, and hemoglobin A1C (HbA1C). Results: Diabetes mellitus (DM) was relatively higher in the age group of 51–60 years with female preponderance. Ethnic distribution demonstrated a high percentage of DM among the Sikkimese Nepalese, followed by Bhutias, and Lepchas. On ascertaining the effects of BNP and hs-CRP on the likelihood that the diabetic participants have CVD, only BNP demonstrated statistical significance. However, unlike hs-CRP, BNP exhibited no association with HbA1C and lipid parameters. BNP and hs-CRP levels were higher among diabetics with CVD when compared to diabetics without CVD. Conclusion: Increasing BNP levels in diabetes is associated with an increased likelihood of exhibiting CVD but increasing hs-CRP level may not be associated with an increased likelihood of exhibiting CVD. Increase in BNP levels independent of influence by HbA1C and lipid profile should be investigated further and yet importantly diabetes with CVD exhibits extra inflammatory load (hs-CRP) comparedto diabetes without CVDs.