Elevated B-type Natriuretic Peptide Research Articles

B-Type Natriuretic Peptide Inhibits the Expression and Function of SERCA2a in Heart Failure.

B-type natriuretic peptide (BNP) possesses protective cardiovascular properties; however, there has not been sufficient serious consideration of the side effects of BNP. As for sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), it was once considered a new target for the treatment of heart failure (HF). Nevertheless, clinical trials of SERCA2a gene therapy in HF have finally become unsuccessful. Research has found that elevated BNP levels and decreased SERCA2a expression are two important HF characteristics, which are always negatively correlated. We hypothesize that BNP inhibits SERCA2a expression and, therefore, exerts negative effects on SERCA2a expression and function.The effects of BNP on endogenous SERCA2a expression and function were tested in mice with HF induced by transverse aortic constriction and neonatal rat cardiomyocytes (NRCM). Furthermore, to verify the effects of BNP on exogenous SERCA2a gene transduction efficacy, BNP was added to the myocardium and cardiomyocytes infected with an adenovirus overexpressing SERCA2a.In vivo, BNP levels were increased, SERCA2a expression was reduced in both the BNP intervention and HF groups, and BNP reduced the overexpressed exogenous SERCA2a protein in the myocardium. Our in vitro data showed that BNP dose-dependently inhibited the total and exogenous SERCA2a expression in NRCM by activating the cGMP-dependent protein kinase G. BNP also inhibited the effects of SERCA2a overexpression on Ca2+ transience in NRCM.The expression and function of endogenous and exogenous SERCA2a are inhibited by BNP. The opposite relationship between BNP and SERCA2a should be given serious attention in the treatment of HF via BNP or SERCA2a gene therapy.

Myocardial Injury by COVID-19 Infection Assessed by Cardiovascular Magnetic Resonance Imaging - A Prospective Multicenter Study.

This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR).Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis. This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

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 non-histaminergic itch in mice. It was also shown that elevated serum BNP is linked to increased pruritus in non-diabetic hemodialysis patients. This study examined plasma BNP levels of 77 patients and N-Terminal pro-BNP (NT-proBNP) levels of 33 patients with differing types of chronic itch to see if BNP and NT-proBNP levels can correlate with itch severity. Plasma BNP and NT-proBNP levels of all itch patients correlated to itch NRS, and in particular for patients with Chronic Pruritus of Unknown Origin (CPUO). Based on this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by IV or osmotic pump induced significant scratching. Additionally, pharmacological and ablation strategies determined that BNP acts centrally by activating the natriuretic peptide receptor A (NPRA) in the dorsal horn of the spinal cord. These data support that BNP and NT-proBNP levels are associated with chronic itch and may be used in clinical setting.

Subclinical myocardial damage after anthracycline chemotherapy in Japanese patients with breast cancer

BackgroundData on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited. MethodWe evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels. ResultsCTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period. ConclusionsApproximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required.

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.

The significance of B-type natriuretic peptide in predicting early mortality among pulmonary embolism patients, alongside troponin: insights from a multicentric registry

BackgroundEarly mortality assessment in acute pulmonary embolism (PE) is crucial for treatment decisions. The role of natriuretic peptides in this context is debated. This study explores elevated B-type natriuretic peptide (BNP) levels, relative to the upper normal limit (UNL), predicting mortality in PE, comparing with troponin (Tn). MethodologyA multicenter PE registry analyzed predictive values for early mortality risk using BNP and Tn, based on proportional elevation to the UNL. Patients followed current PE guidelines. ResultsAmong 1677 PE patients, BNP's AUC exceeded Tn for all-cause (0.727 vs. 0.614) and PE-related mortality (0.785 vs. 0.644), though nonsignificant. BNP's cutoff was 3.5 times UNL for both all-cause and PE-related mortalities; Tn cutoffs were 1.38 and 1.23 times UNL, respectively. ConclusionElevated BNP relative to UNL significantly predicts all-cause and PE-related mortality. While akin to Tn, BNP merits consideration in assessing acute PE risk, especially in intermediate-high-risk cases.

B-type natriuretic peptide levels at admission predictthe prognosis of patients with infective endocarditis undergoing cardiac surgery.

Purpose: The objective of this study was to explore the relationship between elevated B-type natriuretic peptide (BNP) levels and the prognosis of patients with infective endocarditis (IE) undergoing cardiac surgery. Methods: In total, 162 IE patients with recorded BNP levels upon admission were included in the present study. The primary end point was all-cause mortality. Results: Multivariate Cox analysis revealed a significant association between log BNP and all-cause mortality. Kaplan-Meier analysis revealed a poorer prognosis for patients with BNP levels ≥ the 75th percentile. Furthermore, the linear trend test indicated a significant link between BNP quartiles and the primary end point within the models. Conclusion: Elevated BNP levels upon admission could predict all-cause mortality in IE patients undergoing cardiac surgery.

Dysbiotic microbiome induce cardiac impairment by attenuating brain-derived neurotrophic factor in inflammatory bowel diseases

Abstract Background &amp; Aims Mounting evidence suggests that inflammatory bowel disease (IBD) is associated with increased incidences of cardiovascular diseases (CVD), including myocardial infarction and heart failure. However, the molecular mechanisms by which IBD predisposes patients to CVD are poorly understood. This study aimed to identify the role of dysbiosis in gut-heart crosstalk. Methods Chronic colitis-induced cardiac impairment was assessed in mice subjected to dextran sodium sulfate (DSS), rats treated with trinitrobenzenesulfonic acid, and IL10-/-mice which develop spontaneous colitis after weaning. Fecal microbiota of wild type or IL10-/- mice were transplanted to C57BL/6J mice treated with microbiome-depleting antibiotic cocktail and germ-free mice to determine if dysbiosis afflicts the heart. Heart function was evaluated by echocardiography. Heart transcriptomes were profiled by RNA-sequencing. Gut microbiota profiling was performed by 16S rRNA sequencing. Adverse effect of brain-derived neutrophic factor (BDNF) deficiency on the heart was evaluated in cardiac-specific BDNF knockout mice (BdnfΔheart). Results Impairment of heart function, evidenced by decreased left ventricle ejection fraction (LVEF), increased LV mass, and elevated serum B-type natriuretic peptide, was observed in all 3 models of colitis, providing direct evidence that chronic colitis deteriorates the heart (Figure 1). RNA-sequencing revealed loss of Bdnf and alterations of multiple genes critical to heart homeostasis in the myocardium. Many of the changes, including Bdnf reduction, were found in microbiota-depleted C57BL/6J mice and germ-free mice received dysbiotic fecal microbiome, compared to controls, suggesting that dysbiosis impaired the heart by suppressing Bdnf. BdnfΔheart mice had impaired heart function, including decreased contractility and EF, increased fibrosis, and impaired coronary microcirculation (lower CD31), compared to Bdnf[2lox] mice. Mechanistically, miR-155 in the heart and exosomal miR-29b in the plasma were significantly elevated by chronic colitis. miR-155 and miR-29b mimics suppressed BDNF in cardiomyocytes both in vitro and in vivo. Administration of miR-155 inhibitors or exosomes packaged with miR-29b antagonists ameliorated BDNF reduction in the heart of IL10-/- mice. BDNF supplementation markedly improved heart function in DSS mice. Conclusions Chronic colitis impairs the heart through dysbiosis/miR-29b/miR-155/BDNF signaling axis. Targeting this pathway is a promising strategy to overcome gut dysbiosis harmful for the heart in IBD.

The classification shifting and outcomes of DELIVER-type patients with acute heart failure and preserved ejection fraction

Abstract Background The DELIVER trial enrolled subjects with acute heart failure (AHF) and preserved ejection fraction (HFpEF) who had elevated biomarkers and cardiac structural abnormalities. Given the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in AHF, it is important to understand the differences between DELIVER-type and non-DELIVER-type patients and how their classification may shift over time. Method This study enrolled patients hospitalized for AHF with LVEF ≥ 50%. Patients with elevated N-terminal pro B-type natriuretic peptide (NT-proBNP ≥ 300 or 600 pg/mL, depending on cardiac rhythm) and cardiac structural abnormalities (enlarged left atrial volume or index, or left ventricular hypertrophy) were classified as DELIVER-type. Patients who did not meet these criteria were classified as non-DELIVER-type. Patients with estimated glomerular filtration rate ≤ 25 mL/min/1.73m2 and those receiving SGLT2i treatment were excluded. Echocardiographic variables were obtained pre-discharge and one year after the index day. All-cause mortality and heart failure hospitalization up to one year were determined by web-based electronic record. Result The study included 385 subjects with an average age of 83.7 ± 13.9 years, of whom 53.2% were men. The DELIVER-type group had a higher proportion of atrial fibrillation, larger left atrial volume, thicker left ventricular wall, higher levels of the ratio of early diastolic mitral inflow velocity to early diastolic medial mitral annulus velocity (medial mitral E/e'), and higher pulmonary artery systolic pressure (PASP), as well as more evident haemoconcentration and body weight reduction during hospitalization. Kaplan-Meier curve analysis revealed higher rates of all-cause mortality and hospitalization for heart failure at one year in patients with DELIVER-type (Figure 1). In Cox regression analysis, the DELIVER-type subjects had comparable clinical outcomes after accounting for factors such as age, gender, atrial fibrillation, haemoglobin levels, and estimated glomerular filtration rate, compared to non-DELIVER subjects (hazard ratio and 95% confidence interval of mortality [1.62 (0.81-3.25)]). In one-year follow-up, 41.7% of patients shifted from non-DELIVER type to DELIVER-type, but only 14.6% of DELIVER-type subjects had classification shifting. Conclusion Non-DELIVER-type subjects had modestly lower event rates compared to those with DELIVER-type. The high proportion of classification shifting from non-DELIVER-type to DELIVER-type suggested that eligibility could vary during follow-up and that these patients could benefit from SGLT2i therapy.Baseline characteristicsClass shifting in DELIVER type

Abstract 13612: Association Between B-Type Natriuretic Peptide and Inferior Vena Cava Diameter as a Measure of Hypovolemia in Cancer Patients

Introduction: Hypovolemia is frequently seen in cancer patients due to catabolism, cachexia, and decreased oral intake. However, volume status assessment in this population is often difficult due to competing comorbid conditions such as edema. Elevated B-type natriuretic peptide (BNP) is an established biomarker of myocardial wall stress in patients with hypervolemia. We sought to determine if very low BNP could be an objective marker of hypovolemia in cancer patients Hypothesis: In cancer patients undergoing treatment, is low BNP level (&lt;10 pg/mL) associated with small inferior vena cava (IVC) diameter (&lt; 1.4 cm) - an established marker of hypovolemia on transthoracic echocardiography (TTE)?We hypothesize that BNP &lt;10 pg/mL is associated with small IVC as a marker of hypovolemia in cancer patients. Methods: We conducted a retrospective study (N=91) with solid malignancies, undergoing chemo- and/or radiation therapy (RT), divided into 3 groups based on BNP values in pg/mL: low (BNP &lt;10), normal (BNP 10-100) and high (BNP&gt;100). Retrospective data were obtained between 2016-2023 from Rush University Medical Center Cardio-Oncology Registry. IVC measurements by 2 medial trainees (Cohen’s intraclass correlation coefficient = 0.87, p &lt; 0.01) were acquired from formal TTEs obtained within 1 week of BNP measurements. Linear regression was used to calculate the adjusted means (for age, sex, BMI, blood pressure, creatinine, RT, TSH) of the 2 measured IVC diameters per datapoint. Mean difference in IVC diameters was compared between the 3 BNP groups. Results: The population mean age was 59.99 ± 12.19, 67% women. Adjusted mean IVC measurements were 1.89cm, 1.55cm, and 1.26cm for the high, normal, and low BNP groups respectively. The mean difference in IVC diameters between high and low BNP groups was 0.628 ±0.164 cm (p&lt;0.01). Conclusions: In cancer patients undergoing treatment, very low BNP (&lt;10pg/mL) was associated with small IVC as a marker of hypovolemia. In this group of patients, BNP measured with routine lab data is a readily available tool to identify individuals with hypovolemia where other measures of volume status such as physical exams might be uncertain.

Abstract 15115: Efficacy and Safety of miR-132 Inhibitor CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction: Rationale for and Design of the HF-REVERT Trial

Background: Inhibition of miR-132 effectively prevents and reverses heart failure (HF) in relevant models, making it an attractive HF target. CDR132L is a synthetic antisense oligonucleotide (ASO) selectively blocking miR-132. Translational in vitro and in vivo studies have demonstrated meaningful efficacy of CDR132L on left ventricular (LV) structure and function. CDR132L was safe and well tolerated in a Phase 1b study in chronic HF patients. The indicative effects of the miR-132 inhibitor CDR132L may be particularly beneficial in patients with active adverse remodelling, e.g. after acute myocardial infarction with early decline in ejection fraction. These patients have been relatively understudied and therapeutic options are limited. Method: The HF-REVERT (P h ase 2, Multicenter, Randomized, Parallel, 3-arm, Placebo-controlled Study to Assess E f ficacy and Safety of CD R 132L in Pati e nts with Reduced Left V entricular E jection F r ac t ion (≤ 45%) after Myocardial Infarction; NCT05350969) is a proof-of-concept study to evaluate the efficacy of CDR132L in improving cardiac function and safety in patients with reduced LV ejection fraction (LVEF). HF-REVERT aims to assess the efficacy and safety of 5 mg/kg and 10 mg/kg CDR132L, given as 3 single intravenous doses administered 28 days apart as an add-on to standard-of-care treatment, in a larger cohort of patients (N = 280) with HF and reduced LVEF (≤ 45%) after MI with a follow-up of 10 months. Key inclusion criteria are the diagnosis of acute STEMI/NSTEMI and the development of systolic dysfunction (LVEF ≤ 45%) after MI index event and elevated N-terminal pro B-type natriuretic peptide (NT-proBNP). The study consists of a 6-month double-blind treatment period with a read out of the primary endpoint LVESVI (left ventricular end systolic volume index) followed by a 6-month open label observation period. Discussion: The HF-REVERT trial currently tests CDR132L in patients with MI and systolic dysfunction. This trial may therefore underpin the concept of miR-132 inhibition to prevent/reverse cardiac remodeling in HF patients. The results will inform the design of a subsequent outcome trial to test the effect of CDR132L in HF patients.

Abstract 14091: Subclinical Cardiac Dysfunction in the Patients Treated With Anthracycline-Containing Chemotherapy in the Chronic Phase

Background: Anthracycline-induced cardiotoxicity is a concerning problem in the treatment of a variety of cancers. The highest incidence of anthracycline-induced cardiotoxicity was observed during the first year after the completion of chemotherapy, but the changes in cardiac function and biomarkers after the first year have not been adequately investigated. Methods: We analyzed 105 consecutive patients who were followed up for 24 months after starting anthracycline-containing chemotherapy in our hospital from June 2018 to April 2021. Echocardiography and blood test for troponin I and B-type natriuretic peptide (BNP) were performed at baseline, 3 months, 6 months, 12 months, and 24 months after starting the chemotherapy. Results: The cancer types included 71 breast cancers, 18 hematologic cancers, 11 gynecologic cancers, and 5 soft tissue tumors. Compared to baseline, troponin I levels were increased at 3 months (0.011±0.007 ng/ml vs. 0.021±0.021 ng/ml, P&lt;0.05) and 6 months (0.023±0.047 ng/ml, P&lt;0.001), then, recovered to baseline levels. In contrast, BNP levels remained unchanged for 12 months but increased at 24 months compared to baseline (31.9 [5.8-625.7] pg/ml vs. 15.5 [5.8-89.2] pg/ml, P&lt;0.01). In addition, the left ventricular ejection fraction was decreased from baseline to 6 months (65.4±4.8% vs. 63.6±4.5%, P&lt;0.05) and 24 months (63.6±4.7%, P&lt;0.05). Multivariate logistic analysis revealed that age (OR 1.049, 95% CI [1.006-1.097], P=0.029) and total anthracycline dose (OR 1.011, 95% CI [1.002-1.022], P=0.026) were predicting factors for elevated BNP levels above the normal range (&gt;18.2 pg/ml) at 24 months. Conclusion: Subclinical cardiac dysfunction was developed after more than one year. Long-term follow-up is desirable to detect cardiac dysfunction in patients treated with anthracycline-containing chemotherapy.

Remote management of worsening heart failure to avoid hospitalization in a real-world setting.

From a patient and health system perspective, managing worsening heart failure (WHF) as an outpatient has become a priority. Remote management allows early detection of WHF, enabling timely intervention with the aim of preventing hospitalization. The objective of the study was to evaluate the feasibility and safety of remotely managing WHF events using a multiparametric platform. All patients enrolled in the heart failure remote management programme of the Bordeaux University Hospital Telemedicine Center between 1 January and 31 December 2021 were included in the study. Follow-up data were collected until 1 March 2022. Inclusion criteria were chronic heart failure (HF) with New York Heart Association ≥II symptoms and an elevated B-type natriuretic peptide (BNP>100pg/mL or N-terminal-pro-BNP>1000pg/mL). Patient assessments were performed remotely and included measurements of body weight, blood pressure, heart rate, symptoms, biochemical parameters, and data from cardiac implantable electronic devices when available. In total, 161 patients (71±11years old, 79% male) were followed for a mean of 291±66days with a mean adherence to the remote monitoring system of 80±20%. Over this period, 52 (32.3%) patients had 105 WHF events, of which 66 (63%) were successfully managed remotely, the remaining requiring hospitalization. Freedom from WHF events and hospitalization at 300days were 66% and 85%, respectively (P<0.001 for the difference). Increased level of BNP was associated with an increased risk of WHF event [hazard ratio (HR) per unit increase in BNP: 1.001; 95% confidence interval (CI) 1-1.002; P=0.001] and hospitalization (HR 1.002; 95% CI 1.002-1.003; P=0.002). A decrease in the level of glomerular filtration rate was associated with an increased risk of hospitalization (HR per unit decrease in estimated glomerular filtration rate: 0.946; 95% CI 0.906-0.989; P=0.014). WHF event recurrence and (re)hospitalization rates at 1-month were similar among patients managed remotely (18% and 12%, respectively) and those requiring hospitalization (21% and 10%, respectively). Iatrogenic complications occurred more often during hospitalization than remote management (26% vs. 3%, P<0.001). Our study suggests that remote management of WHF events based on a multiparametric approach led by a telemedical centre is feasible and safe. Adopting such a strategy for patients with chronic HF could reduce HF-related hospitalizations with expected benefits for patients, care providers, and health care systems.

Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis.

Rheumatoid arthritis is a prototypic inflammatory condition with affected patients being at greater risk of incident heart failure (HF). Targeting innate immune cell function in the pathogenesis of HF bears the potential to guide the development of future therapies. A collagen-induced arthritis (CIA) model in DBA/1 J mice was used to generate arthritis. Mice with CIA developed concentric hypertrophic myocardial remodeling, left ventricular (LV) diastolic dysfunction, and HF with elevated plasma B-type natriuretic peptide levels but preserved LV ejection fraction. Key features of HF in CIA were increased infiltration of activated neutrophils, deposition of neutrophil extracellular traps in the myocardium, and increased tissue levels of the proinflammatory cytokine IL-1β. Specific inhibition of protein arginine deiminase 4 (PAD4) by an orally available inhibitor (JBI-589), administered after the onset of clinical arthritis, prevented HF with reduced neutrophil infiltration. We identify PAD4-mediated neutrophil activation and recruitment as the key thromboinflammatory pathway driving HF development in arthritis. Targeting PAD4 may be a viable therapeutic approach for the prevention of HF secondary to chronic inflammation.

Elevated Cardiac Biomarkers, Erectile Dysfunction, and Mortality in U.S. Men: NHANES 2001 to 2004

BackgroundThe prevalence of elevated cardiac biomarkers and their link to mortality in men with erectile dysfunction in the U.S. population are unknown. ObjectivesThe purpose of this study was to evaluate the prevalence of elevations in N-terminal prohormone B-type natriuretic peptide, high sensitivity troponin (hs-troponin) T, and 3 hs-troponin I assays and their associations with mortality in U.S. men with and without erectile dysfunction. MethodsWe conducted cross-sectional analyses using logistic regression to examine associations of elevated cardiac biomarkers (>90th percentile) with erectile dysfunction in 2,971 male participants aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. We conducted prospective analyses using Cox regression to examine the mortality implications of elevations in cardiac biomarkers in the setting of erectile dysfunction. ResultsElevations in hs-troponin T and the 3 hs-troponin I assays were associated with erectile dysfunction, with the strongest association for hs-troponin T (adjusted OR: 2.01; 95% CI: 1.22-3.30). Elevated N-terminal prohormone B-type natriuretic peptide was not significantly associated with erectile dysfunction (OR: 1.22; 95% CI: 0.74-2.03). There were 673 deaths during a median of 16 years of follow-up. Men with erectile dysfunction were at an elevated risk of death (adjusted HR: 1.23; 95% CI: 1.04-1.46). Those men with elevated cardiac biomarkers in the setting of erectile dysfunction were at highest risk of all-cause and cardiovascular mortality (adjusted HRs ranging from ∼1.5 to 2.4). ConclusionsIn this national study, the association of erectile dysfunction with elevated hs-troponin and excess mortality risk suggests that men with erectile dysfunction should be evaluated and targeted for intensive cardiovascular risk management.

Long-term dietary n3 fatty acid prevents aging-related cardiac diastolic and vascular dysfunction

AimsThe prevalence of left ventricular (LV) diastolic and vascular dysfunction increases with age, eventually leading to heart failure with preserved ejection fraction (HFpEF). A preventive strategy is an unmet medical need. We and others reported previously on the beneficial effects of omega-3 fatty acid alpha linolenic acid (ALA) on cardiovascular disorders in animal models and translational studies. We now investigate whether long-term dietary ALA could prevent LV diastolic dysfunction and vascular aging in a murine model. Methods and resultsWild-type C57BL/6 J mice were fed a chow or ALA diet for 12 months, starting at 6 months of age. Here, we show that aged (~18 months) mice recapitulate major hallmarks of HFpEF, including LV diastolic dysfunction with preserved ejection fraction, impaired vascular function, cardiac fibrosis, arterial stiffening and inflammation, as well as elevated B-type natriuretic peptide (BNP). Long-term ALA supplementation upregulated the mitochondrial tricarboxylic acid enzyme Idh2 and the antioxidant enzymes SOD1 and Gpx1. It also has been associated with reduced inflammation and ECM remodeling, accompanied by a significant downregulation of fibrosis biomarkers MMP-2 and TGF-β in both cardiac and vascular tissues obtained from aged mice. Our data exhibited the preventive effects of dietary ALA against LV diastolic dysfunction, impaired vasorelaxation, cardiac fibrosis, inflammation and arterial stiffening in aged mice. ConclusionsWe provide evidence and a simplified mechanistic insight on how long-term ALA supplementation is a successful strategy to prevent the development of age-related diastolic and vascular dysfunction.

Severity of functional tricuspid regurgitation is associated with mortality in patients with pulmonary hypertension in long-term follow-up.

Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic state present in many cardiovascular, respiratory, and systemic diseases. PH is considered to have a higher risk of cardiovascular events and mortality. The most common type of functional tricuspid regurgitation (FTR) is associated with PH. The aim of this study was to evaluate the association between FTR severity and mortality in PH in western China. This is a retrospective analysis in PH patients and all patients underwent right-heart catheterization (RHC) for hemodynamic measurements. The FTR severity was determined according to the guidelines. Uni- and multivariate analyses were used to identify risk factors for mortality. From 2015 to 2021, 136 patients with PH with a median age of 50 years (interquartile range [IQR]: 35-64 years). During 26-month median follow-up (mean 27.7 ± 15.1 months), 40 (29.2%) patients died (mean after 21.7 ± 14.1 months). In the univariate Cox regression analysis, World Health Organization functional class (WHO FC) III/IV, elevated B-type natriuretic peptide, pulmonary vascular resistance (≥16.2 Wood units), pulmonary artery oxygen saturation, severe FTR and right ventricular diameter/left ventricular diameter (≥0.62) were significantly associated with mortality. In the multivariate Cox regression analysis, severe FTR, WHO FC III/IV, and right ventricular end-diastolic pressure (RVEDP) were risk factors for mortality. Severe FTR at baseline was strongly associated with mortality in both precapillary and postcapillary PH patients, independent of the other risk factors as RVEDP,HO FC III/IV,optimal pulmonary arterial hypertension targeted therapy.

Prevalence and Predictors of Cardiogenic Shock in Intermediate-Risk Pulmonary Embolism: Insights From the FLASH Registry

BackgroundPatients with acute pulmonary embolism (PE) and hypotension (high-risk PE) have high mortality. Cardiogenic shock can also occur in nonhypotensive or normotensive patients (intermediate-risk PE) but is less well characterized. ObjectivesThe authors sought to evaluate the prevalence and predictors of normotensive shock in intermediate-risk PE. MethodsIntermediate-risk PE patients in the FLASH (FlowTriever All-Comer Registry for Patient Safety and Hemodynamics) registry undergoing mechanical thrombectomy with the FlowTriever System (Inari Medical) were included. The prevalence of normotensive shock (systolic blood pressure ≥90 mm Hg but cardiac index ≤2.2 L/min/m2) was assessed. A composite shock score consisting of markers of right ventricular function and ischemia (elevated troponin, elevated B-type natriuretic peptide, moderately/severely reduced right ventricular function), central thrombus burden (saddle PE), potential additional embolization (concomitant deep vein thrombosis), and cardiovascular compensation (tachycardia) was prespecified and assessed for its ability to identify normotensive shock patients. ResultsOver one-third of intermediate-risk PE patients in FLASH (131/384, 34.1%) were in normotensive shock. The normotensive shock prevalence was 0% in patients with a composite shock score of 0 and 58.3% in those with a score of 6 (highest score). A score of 6 was a significant predictor of normotensive shock (odds ratio: 5.84; 95% CI: 2.00-17.04). Patients showed significant on-table improvements in hemodynamics post-thrombectomy, including normalization of the cardiac index in 30.5% of normotensive shock patients. Right ventricular size, function, dyspnea, and quality of life significantly improved at the 30-day follow-up. ConclusionsAlthough hemodynamically stable, over one-third of intermediate-risk FLASH patients were in normotensive shock with a depressed cardiac index. A composite shock score effectively further risk stratified these patients. Mechanical thrombectomy improved hemodynamics and functional outcomes at the 30-day follow-up.

Aortic Stenosis: Risk Stratification and Timing of Surgery.

This review summarizes the current management of patients with newly diagnosed aortic stenosis. Recent developments include detection of early myocardial dysfunction using serum B-type natriuretic peptide levels and global longitudinal strain, as well as ongoing trials of transcatheter aortic valve replacement in asymptomatic patients and patients with moderate aortic stenosis complicated by symptoms or left ventricular systolic dysfunction. Given the high mortality associated with severe symptomatic aortic stenosis, all symptomatic patients should be referred for aortic valve replacement. Asymptomatic patients with left ventricular systolic dysfunction, abnormal exercise stress test, high degree of stenosis, rapid disease progression, or elevated serum B-type natriuretic peptide level may also have an indication for valve replacement, based on established criteria. The progress in management of severe aortic stenosis has been in the direction of earlier detection and earlier valve replacement.

Elevated B-type natriuretic peptide level expression associated with acute myocardial infarction patients in Jammu population (India)

B-type natriuretic peptide (BNP) is a highly sensitive and specific indicator of the size of myocardial infarction, which can help in assessing the degree of cardiovascular risk. Elevated BNP levels in patients hospitalized for acute myocardial infarction (AMI) are associated with heart failure and mortality, and the measurements of BNP in a short-term period could be helpful to predict the future events. The role of short-term follow-up BNP level has not been established in the patients with AMI. This retrospective study was conducted on the patients admitted to the Government Medical College, Jammu (India). The analysis of blood EDTA sample was analysed for BNP and this test was performed by using a fully automated random access immunoassay analyser whose principle is based on micro-particle enzyme immunoassay (MEIA). The reference range of BNP is 0-100 pg mL-1. The study revealed a 90% BNP increase in AMI patients in comparison to the 10% increase in normal healthy ones. However, BNP showed elevated levels in healthy individuals suffering from renal insufficiency. The BNP was > 100 pg mL-1 in the majority of AMI patients while in controls BNP is <100 pg mL-1.