Brain Natriuretic Peptide Levels Research Articles

Nonplatelet thromboxane generation is associated with impaired cardiovascular performance and mortality in heart failure.

Nonplatelet thromboxane generation, stimulated largely by oxidative stress, is a novel mortality risk factor in individuals with coronary artery disease. Though inversely associated with left ventricular ejection fraction (LVEF), a potential role in the pathobiology of heart failure (HF) remains poorly defined. Nonplatelet thromboxane generation and oxidative stress were assessed by measuring urine thromboxane-B2 metabolites (TXB2-M) and 8-isoPGF2α by ELISA in 105 subjects taking aspirin and undergoing right heart catheterization for evaluation of HF, valve disease, or after transplantation. Multivariable logistic regression and survival analyses were used to define associations of TXB2-M to invasive measures of cardiovascular performance and 4-year clinical outcomes. TXB2-M was elevated (>1,500 pg/mg creatinine) in 46% of subjects and correlated with HF severity by New York Heart Association (NYHA) functional class and brain natriuretic peptide level, modestly with LVEF, but not with HF etiology. There was no association of oxidative stress to HF type or etiology but a trend with NYHA functional class. Multiple invasive hemodynamic parameters independently associated with TXB2-M after adjustment for oxidative stress, age, sex, and race with pulmonary effective arterial elastance (Ea pulmonary), reflective of right ventricular afterload, being the most robust on hierarchical analysis. Similar to Ea pulmonary, elevated urinary TXB2-M is associated with increased risk of death (adjusted HR = 2.15, P = 0.037) and a combination of death, transplant, or mechanical support initiation (adjusted HR = 2.0, P = 0.042). Nonplatelet TXA2 thromboxane generation is independently associated with HF severity reflected by invasive measures of cardiovascular performance, particularly right ventricular afterload, and independently predicted long-term mortality risk.NEW & NOTEWORTHY Nonplatelet thromboxane generation in heart failure is independently associated with risk of death, transplant, or need for mechanical support. Measurement of urine thromboxane metabolites using a clinically available assay may be a useful surrogate for invasive measurement of cardiovascular hemodynamics and performance that could provide prognostic information and facilitate tailoring of therapy in patients with heart failure. Inhibiting thromboxane generation or its biological effects is a potential strategy for improving cardiovascular performance and outcomes in heart failure.

Unmasking Myocardial Dysfunction in Patients Hospitalized for Community-Acquired Pneumonia Using a 4-Chamber 3-Dimensional Volume/Strain Analysis.

Lower respiratory infection was reported as the most common fatal infectious disease. Community-acquired pneumonia (CAP) and myocardial injury are associated; yet, true prevalence of myocardial injury is probably underestimated. We assessed the rate and severity of myocardial dysfunction in patients with CAP. Admitted patients diagnosed with CAP were prospectively recruited. All the patients had C-reactive protein (CRP), brain natriuretic peptide (BNP), and high-sensitivity cardiac troponin (hs-cTnl) tests added to their routine workup. 2D/3D Doppler echocardiography was done on a Siemens Acuson SC2000 machine ≤ 24 h of diagnosis. 3D datasets were blindly analyzed for 4-chamber volumes/strains using EchobuildR 3D-Volume Analysis prototype software, v3.0 2019, Siemens-Medical Solutions. Volume/strain parameters were correlated with admission clinical and laboratory findings. The cohort included 34 patients, median age 60 years (95% CI 55–72). The cohort included 18 (53%) patients had hypertension, 9 (25%) had diabetes mellitus, 7 (21%) were smokers, 7 (21%) had previous myocardial infarction, 4 (12%) had chronic renal failure, and 1 (3%) was on hemodialysis treatment. 2D/Doppler echocardiography findings showed normal ventricular size/function (LVEF 63 ± 9%), mild LV hypertrophy (104 ± 36 g/m2), and LA enlargement (41 ± 6 mm). 3D volumes/strains suggested bi-atrial and right ventricular dysfunction (global longitudinal strain RVGLS = − 8 ± 4%). Left ventricular strain was normal (LVGLS = − 18 ± 5%) and correlated with BNP (r = 0.40, p = 0.024). The patients with LVGLS > − 17% had higher admission blood pressure and lower SaO2 (144 ± 33 vs. 121 ± 20, systolic, mmHg, p = 0.02, and 89 ± 4 vs. 94 ± 4%, p = 0.006, respectively). hs-cTnl and CRP were not different. Using novel 3D volume/strain software in CAP patients, we demonstrated diffuse global myocardial dysfunction involving several chambers. The patients with worse LV GLS had lower SaO2 and higher blood pressure at presentation. LV GLS correlated with maximal BNP level and did not correlate with inflammation or myocardial damage markers.

Serum miR-204 and miR-451 Expression and Diagnostic Value in Patients with Pulmonary Artery Hypertension Triggered by Congenital Heart Disease.

Objective To determine the level of expression and clinical importance of serum miR-204 and miR-451 in patients with pulmonary arterial hypertension caused by congenital heart disease (CHD-PAH). Methods From July 2019 to January 2021, 114 infants with congenital heart disease (CHD) were hospitalized at Qingdao's Fuwai Cardiovascular Hospital. They were grouped into categories: CHD (53 cases) and CHD-PAH (61 cases) based on whether they had pulmonary hypertension (PAH). In addition, 60 healthy children were selected as the control group. All children underwent routine biochemical examination, echocardiography, and pulmonary arterial pressure examination. By using an enzyme-linked immunosorbent assay (ELISA), the levels of brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA) in the blood were measured. Additionally, reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of miR-204 and miR-451 in peripheral blood. The correlation between miR-204, miR-451, BNP, ADMA, and mPAP was investigated using Pearson correlation analysis. Results Consequently, the TC, BNP, and ADMA serum levels were considerably higher in the CHD and CHD-PAH groups than in the control group (P < 0.05), whereas BNP and ADMA serum levels were significantly higher in the CHD-PAH group than in the CHD group (P < 0.05). According to RT-PCR data, the expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD and CHD-PAH groups were significantly lower (P < 0.05) when compared to the control group. The expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD-PAH group were substantially lower (P < 0.05) than in the CHD group. Significantly, the findings of the ROC curve revealed that the area under the curve (AUC) of CHD-PAH diagnosed by miR-204 and miR-451 alone was 0.737 and 0.725, respectively, and the AUC of joint diagnosis was 0.840, which was greater than that of single diagnosis (P < 0.05). Patients with CHD-PAH had lower levels of miR-204 and miR-451 in their blood, and this was found to be associated with BNP, ADMA, and mPAP, analyzed by Pearson correlation. Conclusions Children with CHD-PAH can be diagnosed based on aberrant expressions of miR-204 and miR-451 in their peripheral blood serum. Moreover, CHD-PAH can be diagnosed if the combination of miR-204 and miR-451 is detected as a biomarker, which has a higher diagnostic value.

Pharmacological Targeting of Senescence with ABT-263 in Experimental Heart Failure with Preserved Ejection Fraction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fundação Ciência e Tecnlogia HFpEF is the most common form of heart disease in the elderly and is associated with high morbidity and mortality. Our understanding of HFpEF pathophysiology is limited and development of efficient therapies that alter the clinical course of the disease has proved greatly challenging. Although aging is a risk factor of HFpEF1, the involvement of aging hallmarks such as cell senescent and immunosenescence is unclear. Recently, a link between endothelial senescence and HFpEF development was demonstrated in mice with accelerated aging [1], endorsing anti-aging pharmacologic as potential new therapeutic alternatives for HFpEF. In fact, the senolytic (drugs that selectively promote apoptosis of senescent cells) ABT-263 has already proven efficacy in the context of cardiovascular diseases. Further studies are needed to clarify the relevance of aging and of anti-aging therapies in the context of HFpEF. Using ZSF1 obese rats (ZSF1-Ob) as model of HFpEF we showed from 18 weeks signs of immunosenescence compared to ZSF1-Ln, namely an increased frequency of circulating myeloid cells and decreased frequency of T and B cells. Concomitantly, expression of pro-inflammatory factors (IL-6, IL-1, TGF-β, TNF-α) was upregulated in peripheral blood mononuclear cells (PBMCs) of ZSF1-Ob which also displayed characteristic features of cell senescence (p21 expression, lysosomal endogenous Beta-galactosidase (SA-B-Gal) senescence-associated secretory phenotype (SASP) and up-regulation of BCL-XL. Importantly, no signs of cellular senescence (SA-B-gal, pH2AX and senescence associated pathways) were found in the main hematopoietic organs (spleen and bone marrow). Alongside, these systemic alterations, an upsurge of cellular senescence was observed in myocardium of ZSF1-Ob rats, particularly in endothelial and hematopoietic cells. Serum of ZSF1-Ob rat was able to induce activation and cellular senescence of cardiac microvascular endothelial cells, indicating that systemic circulating factors may be the upstream mechanism of cellular senescence and dysfunction in HFpEF. Analysis of HFpEF patients and a control cohort adjusted to main co-morbidities further demonstrated accumulation of senescent monocytes in HFpEF patients. In these patients, the senescence marker SA-B-Gal correlated with plasmatic brain natriuretic peptide (BNP) levels and pulmonary artery systolic pressure. Targeting aging hallmarks through the treatment of ZSF1-Ob rat with ABT-263 resulted in a reduction in circulating senescent cells, decreased systemic and local inflammation, re-established immune proportions, restore the levels of circulating BNP and attenuated myocardial remodeling, particularly endothelial dysfunction and fibrosis. Collectively these findings support that premature cellular senescence contributes to the establishment of a deleterious pro-inflammatory environment in HFpEF and that senolytic agents hold promise for the treatment of this syndrome.

Pilot Study Investigating Brain Natriuretic Peptide, Troponin, Galectin-3, and miRNA-126a-5p as Biomarkers of Persistent Pulmonary Hypertension in Neonates with Hypoxic-Ischemic Injury Receiving Therapeutic Hypothermia.

The objective was to evaluate the utility of brain natriuretic peptide (BNP), troponin, galectin-3 (Gal-3), and microRNA (miRNA)-126a-5p as screening biomarkers for persistent pulmonary hypertension of the newborn (PPHN) by comparing expression in serum of infants with hypoxic-ischemic injury that develop PPHN to those that do not. This was a prospective, observational pilot study including neonates with hypoxic-ischemic injury undergoing therapeutic hypothermia (TH) at two regional perinatal medical centers. PPHN in this population was diagnosed clinically and confirmed by echocardiogram. Serial measurements of biomarkers were performed from 6 to 96 hours post-TH initiation in 40 patients. Of 40 infants in the study, 10 (25%) developed PPHN and 30 (75%) did not. Baseline demographics and hemodynamics were similar between the groups. Patients with PPHN had a significantly higher need for vasopressors compared with patients without PPHN (70 vs. 27%, p = 0.007). Mean serum BNP and troponin levels were significantly higher in the PPHN group peaking at 12 to 24 hours and decreasing following PPHN treatment initiation. miRNA-126a-5p expression was increased in patients with PPHN compared with patients without, with statistical significance detected at 12 hours (p = 0.005) and 96 hours (p = 0.01). Mean circulating Gal-3 levels were not statistically different between the two groups; however, Gal-3 was elevated in all patients with hypoxic-ischemic injury on TH compared with healthy infants from prior studies. BNP and troponin are readily available, low-cost biomarkers that showed significant serial elevations in the PPHN group of the study and, thus, may have value in screening for PPHN in the setting of hypoxic-ischemic encephalopathy (HIE). Gal-3 was elevated in all patients with HIE and may be a useful biomarker of hypoxic injury in infants being evaluated for TH. Elevations in miRNA-126a-5p were not consistently seen in this study. Larger studies are required to establish an association between PPHN and these biomarkers in patients with and without HIE. · Serum biomarkers of persistent pulmonary hypertension of the newborn. · Serum biomarkers of hypoxic-ischemic injury.

Effectiveness of Proanthocyanidin plus Trimetazidine in the Treatment of Non-Small-Cell Lung Cancer with Radiation Heart Injury.

This study was intended to explore the effect of proanthocyanidin (PC) combined with trimetazidine in non-small-cell lung cancer (NSCLC) with radiation-induced heart damage (RIHD). It was a prospective randomized controlled study that 86 NSCLC patients with radiation treatment in Cangzhou People's Hospital from January 2019 and June 2021 were enrolled and randomized to either the control group or the study group via the random table method, 43 cases in each group. The control group received trimetazidine, and the study group additionally received PC. The incidence of RIHD-related clinical manifestation, RIHD-related ECG, and RIHD-related cardiac ultrasound change were all lower in the study group. After radiotherapy, the serum level of superoxide dismutase (SOD) was higher, and malondialdehyde (MDA) was lower in the study group when compared with the control group. After radiotherapy, the serum levels of brain natriuretic peptide (BNP), cardiac troponin (cTnT), creatine kinase (CK), and creatine kinase isoenzymes (CKMB) were all lower in the study group when compared with the control group. The efficacy of PC plus trimetazidine for NSCLC with RIHD is superior to trimetazidine alone, and it significantly mitigates radiation-induced inflammatory response and oxidative stress.

Brain Natriuretic Peptide Biomarkers in Current Clinical and Therapeutic Scenarios of Heart Failure.

Brain natriuretic peptide (BNP) and its inactive N-terminal fragment, NT-proBNP, are serum biomarkers with key roles in the management of heart failure (HF). An increase in the serum levels of these peptides is closely associated with the pathophysiological mechanisms underlying HF such as the presence of structural and functional cardiac abnormalities, myocardial stretch associated with a high filling pressure and neuro-hormonal activation. As BNP and NT-proBNP measurements are possible, several studies have investigated their clinical utility in the diagnosis, prognostic stratification, monitoring and guiding therapy of patients with HF. BNP and NT-proBNP have also been used as criteria for enrollment in randomized trials evaluating the efficacy of new therapeutic strategies for HF. Nevertheless, the use of natriuretic peptides is still limited in clinical practice due to the controversial aspect of their use in different clinical settings. The purpose of this review is to discuss the main issues associated with using BNP and NT-proBNP serum levels in the management of patients with HF under current clinical and therapeutic scenarios.

Patients phenotypes and cardiovascular risk in type 2 diabetes: the Jackson Heart Study

BackgroundCardiovascular prognosis related to type 2 diabetes may not be adequately captured by information on comorbid conditions such as obesity and hypertension. To inform the cardiovascular prognosis among diabetic individuals, we conducted phenotyping using a clustering approach based on clinical data, echocardiographic indices and biomarkers.MethodsWe performed a cluster analysis on clinical, biochemical and echocardiographic variables from 529 Blacks with diabetes in the Jackson Heart Study. An association between identified clusters and major adverse cardiovascular events (MACE- composite of coronary heart disease, stroke, heart failure and atrial fibrillation) was assessed using Cox proportional hazards modeling.ResultsCluster analysis separated individuals with diabetes (68% women, mean age 60 ± 10 years) into three distinct clusters (Clusters 1,2 &3 - with Cluster 3 being a hypertrophic cluster characterized by highest LV mass, levels of brain natriuretic peptide [BNP] and high-sensitivity cardiac troponin-I [hs-cTnI]). After a median 12.1 years, there were 141 cardiovascular events. Compared to Cluster1, Clusters 3 had an increased risk of cardiovascular disease (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.08, 2.37), while Cluster 2 had a similar risk of outcome (HR 1.11; 95% CI 0.73, 168).ConclusionsAmong Blacks with diabetes, cluster analysis identified three distinct echocardiographic and biomarkers phenotypes, with cluster 3 (high LV mass, high cardiac biomarkers) associated with worse outcomes, thus highlighting the prognostic value of subclinical myocardial dysfunction.

DILATED CARDIOMYOPATHY ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITOR, NIVOLUMAB

TYPE: Case Report TOPIC: Pharmacotherapeutics INTRODUCTION: Cardiomyopathy related to immune checkpoint inhibitor (ICI) is an infrequent adverse event, and the mechanism is still unclear. The most plausible mechanism is via hyper-infiltration of T- cells that damage the myocardial tissue. CASE PRESENTATION: An 88-year-old female with metastatic melanoma receiving treatment with Nivolumab and Talimogene laherparevec (intralesional), presented with of progressive dyspnea for five days. The patient was diagnosed with acute hypoxic respiratory failure secondary to acute heart failure. Initial laboratory values included brain natriuretic peptide (BNP) level of 530 pg/ml, and high sensitivity troponin level of 130 ng/L. Electrocardiogram showed normal sinus rhythm without evidence of acute ST-changes. Computed tomography angiogram of the chest confirmed evidence of bilateral pleural effusions without evidence of pulmonary embolism (Figure 1). Patient underwent left thoracocentesis performed by interventional radiology. Echocardiogram showed LVEF of 20-25% with severe global hypokinesis. Pleural fluid analysis was consistent with transudate. There was no evidence of malignancy on cytology or infection on gram stain. Cardiac magnetic resonance imaging was performed indicating LVEF of 23%, but no evidence of myocarditis or any infiltrative process. Left heart catherization showed no evidence of coronary artery disease. The medical recommendation was to discontinue Nivolumab therapy. DISCUSSION: Our clinical case highlights the importance of long-term follow-up of cancer patients consuming ICI since there are rare cardiac adverse events that presents after several months. Unfortunately, our patient died within 30 days of discharge. CONCLUSIONS: Cardiomyopathy is a rare, but potentially life-threatening complication of ICI therapy and should be considered when discussing treatment modalities with patients, especially the elderly. DISCLOSURE: Nothing to declare. KEYWORD: nivolumab

A Novel Speckle-Tracking Echocardiography Derived Parameter That Predicts Clinical Worsening in Children with Pulmonary Arterial Hypertension

Pulmonary arterial hypertension is a severe, progressive disease in children, that causes right ventricular dysfunction over time. Tissue motion annular displacement is a novel speckle-tracking derived echocardiographic parameter used in assessing ventricular function. The aim of our study was to determine the prognostic value of this echocardiographic parameter in children with pulmonary arterial hypertension. We conducted a case-control study by assessing twenty children with pulmonary arterial hypertension (idiopathic or secondary) and twenty age- and sex-matched controls, using clinical (WHO functional class, 6-min walking test), laboratory (brain natriuretic peptide level) and echocardiographic parameters (conventional and speckle-tracking derived tissue motion annular displacement) at enrolment and after one year of follow-up. According to their WHO functional class altering after one year, the pulmonary arterial hypertension patients were divided into two groups: non-worsening (eleven) and worsening (nine). The conventional echocardiographic parameters and all measured tricuspid tissue motion annular displacement indices (lateral, septal, midpoint and midpoint fractional displacement—TMADm%) were significantly lower in both pulmonary arterial hypertension groups (non-worsening and worsening) compared to controls. Comparing the worsening and non-worsening groups, only the TMADm% and brain natriuretic peptide level was significantly lower in worsening in comparison with non-worsening pulmonary arterial hypertension children (p = 0.010 and p = 0.018, respectively). In receiver-operating characteristic curve analysis, we found a cut-off value of 16.15% for TMADm% and a cut-off value of 34.35 pg/mL for the brain natriuretic peptide level that can predict worsening in pulmonary arterial hypertension children. In conclusion, tricuspid annulus midpoint fractional displacement, an angle-dependent speckle-tracking derived parameter, could be a good additional parameter in the assessment of the longitudinal right ventricular systolic function and in prediction of clinical worsening in children with pulmonary arterial hypertension.

Routine assessment of cardiotoxicity in patients undergoing long-term immune checkpoint inhibitor therapy.

The indications for immune checkpoint inhibitors (ICIs) are expanding in cancer drug therapy, and while cardiac events associated with ICIs are often fatal, there are few reports regarding cardiac complications associated with long-term ICI therapy. We aimed to study cardiac complications in patients undergoing long-term ICI therapy. From the database of our local cardio-oncology unit, we enrolled patients with cancer undergoing ICI therapy for more than 6months and for whom cardiologists continuously performed routine follow-ups. We defined the primary endpoint as discontinuation of ICI due to cardiac events. We also analyzed changes in cardiac biomarkers and echocardiographic parameters. We retrospectively analyzed 55 consecutive patients (43 males, mean age: 65 ± 11years) treated with ICI therapy in our hospital between January 2017 and June 2021. None of the patients discontinued ICI therapy due to cardiac events more than 6months after treatment was initiated. Among the participants, we observed four patients with elevated serum troponin I levels, seven patients with decreased global longitudinal strain values, and two patients with elevated plasma brain natriuretic peptide levels. No patient required drug intervention for these cardiac events; furthermore, there were no cases of clinically diagnosed myocarditis. In the present study, there were no cardiac events causing ICI discontinuation in patients undergo ICI therapy for more than 6months.

Are clinical features and cardiac biomarkers at admission related to severity in pediatric acute myocarditis?: Clinical features and cardiac biomarkers in pediatric acute myocarditis

ObjectivesTo evaluate the factors associated with intensive care requirement and mortality in pediatric myocarditis. MethodsChildren aged 28 days to 18 years who were diagnosed with acute myocarditis in a pediatric emergency department between January 2010 and September 2020 were enrolled in the study retrospectively. Demographic and clinical features, cardiac biomarkers, and imaging findings were evaluated. Length of hospital stay, need for hospitalization in the pediatric intensive care unit (PICU), treatments, and survival outcomes were recorded. To define the severity of disease, three groups were created and the data were compared in terms of clinical, laboratory, and imaging findings. The patients treated in the pediatric ward were compared with those hospitalized in the PICU. Ventricular dysfunction was defined in patients with a left ventricular ejection fraction (LVEF) of <50% and these patients were compared with those who had an LVEF of >50%. Also, survivor and non-survivor patients were compared. ResultsA total number of 62 patients with a median age of 8 years were included. Chest pain and tachycardia were the most common findings on physical examination. The mean LVEF was 59.3 ± 13.0% at admission. Of the patients, 17 were hospitalized in the PICU (27.4%). Chest pain was more common in patients hospitalized in the pediatric ward (p<0.001), and hypotension, vomiting, arrhythmia, were more common and LVEF was lower in patients in the PICU (p = 0.017, p = 0.008, p = 0.006, and p = 0.025, respectively). The children treated in the PICU were younger than those in the pediatric ward (p = 0.009). Troponin I levels were significantly higher in the pediatric ward (p = 0.035), and brain natriuretic peptide (BNP) levels were higher in patients in the PICU (p = 0.012). Death occurred in four patients. Hypotension and vomiting were significantly more common in non-survivors (p = 0.020 and 0.004, respectively). Inotropes and intravenous immunoglobulin (IVIG) were more commonly used in non-survivors (p = 0.001 and p = 0.015, respectively). BNP levels were higher in non-survivors (p = 0.008), and troponin I levels were not different between survivors and non-survivors (p = 0.260). ConclusionIn pediatric acute myocarditis, lower LVEF, increased BNP, as well as the presence of hypotension and arrhythmia were found to be related to intensive care requirement. Hypotension and vomiting were found to be more common in non-survivors. Due to the possibility of rapidly worsening disease, physicians should be alert to the presence of these findings.

Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients

Background and objectivePaclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer.Patients and methodsThis randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann–Whitney U test, and chi-square test.ResultsAs compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9th and 12th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo.ConclusionAlpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer.Trial registrationClinicalTrials.gov: NCT03908528.

Characterization of critically ill patients with septic shock and sepsis-associated cardiomyopathy using cardiovascular MRI.

AimsSepsis‐induced cardiomyopathy is a major complication of septic shock and contributes to its high mortality. This pilot study investigated myocardial tissue differentiation in critically ill, sedated, and ventilated patients with septic shock using cardiovascular magnetic resonance (MR).Methods and resultsFifteen patients with septic shock were prospectively recruited from the intensive care unit. Individuals received a cardiac MR scan (1.5 T) within 48 h after initial catecholamine peak and a transthoracic echocardiography at 48 and 96 h after cardiac MR. Left ventricular ejection fraction was assessed using both imaging modalities. During cardiac MR imaging, balanced steady‐state free precession imaging was performed for evaluation of cardiac anatomy and function in long‐axis and short‐axis views. Native T1 maps (modified Look–Locker inversion recovery 5 s(3 s)3 s), T2 maps, and extracellular volume maps were acquired in mid‐ventricular short axis and assessed for average plane values. Patients were given 0.2 mmol/kg of gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Critical care physicians monitored sedated and ventilated patients during the scan with continuous invasive monitoring and realized breathholds through manual ventilation breaks. Laboratory analysis included high‐sensitive troponine T and N terminal pro brain natriuretic peptide levels. Twelve individuals with complete datasets were available for analysis (age 59.5 ± 16.9 years; 6 female). Nine patients had impaired systolic function with left ventricular ejection fraction (LVEF) < 50% (39.8 ± 5.7%), and three individuals had preserved LVEF (66.9 ± 6.7%). Global longitudinal strain was impaired in both subgroups (LVEF impaired: 11.0 ± 1.8%; LVEF preserved: 16.0 ± 5.8%; P = 0.1). All patients with initially preserved LVEF died during hospital stay; in‐hospital mortality with initially impaired LVEF was 11%. Upon echocardiographic follow‐up, LVEF improved in all previously impaired patients at 48 (52.3 ± 9.0%, P = 0.06) and 96 h (54.9 ± 7.0%, P = 0.02). Patients with impaired systolic function had increased T2 times as compared with patients with preserved LVEF (60.8 ± 5.6 ms vs. 52.2 ± 2.8 ms; P = 0.02). Left ventricular GLS was decreased in all study individuals with impaired LVEF (11.0 ± 1.8%) and less impaired with preserved LVEF (16.0 ± 5.8%; P = 0.01). T1 mapping showed increased T1 times in patients with LVEF impairment as compared with patients with preserved LVEF (1093.9 ± 86.6 ms vs. 987.7 ± 69.3 ms; P = 0.03). Extracellular volume values were elevated in patients with LVEF impairment (27.9 ± 2.1%) as compared with patients with preserved LVEF (22.7 ± 1.9%; P < 0.01).ConclusionsSeptic cardiomyopathy with impaired LVEF reflects inflammatory cardiomyopathy. Takotsubo‐like contractility patterns occur in some cases. Cardiac MR is safely feasible in critically ill, sedated, and ventilated patients using extensive monitoring and experienced staff.Trial Registration: retrospectively registered (ISRCTN85297773)

The association between cardiac involvement and long-term clinical outcomes in patients with Duchenne muscular dystrophy.

AimsDespite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long‐term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long‐term clinical outcomes and their associated factors in patients with late‐stage DMD.Methods and resultsA total of 116 patients with late‐stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all‐cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow‐up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log‐rank P = 0.005). In the multivariable Cox regression analysis, brain‐natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019–1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651–52.148, P = 0.011) were significant predictors of all‐cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log‐rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005–1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704–10.296, P = 0.002) were significant predictors of the composite event in patients with DMD.ConclusionsPatients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late‐stage DMD, irrespective of LVEF.

Tranilast for advanced heart failure in patients with muscular dystrophy: a single-arm, open-label, multicenter study

BackgroundThe transient receptor potential cation channel subfamily V member 2 (TRPV2) is a stretch-sensitive calcium channel. TRPV2 overexpression in the sarcolemma of skeletal and cardiac myocytes causes calcium influx into the cytoplasm, which triggers myocyte degeneration. In animal models of cardiomyopathy and muscular dystrophy (MD), TRPV2 inhibition was effective against heart failure and motor function. Our previous pilot study showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide (BNP) levels in two MD patients with advanced heart failure. Thus, this single-arm, open-label, multicenter study aimed to evaluate the safety and efficacy of tranilast for heart failure.MethodsThe study enrolled MD patients with advanced heart failure whose serum BNP levels were > 100 pg/mL despite receiving standard cardioprotective therapy. Tranilast was administered orally at 100 mg, thrice daily. The primary endpoint was the change in log (BNP) (Δlog [BNP]) at 6 months from baseline. The null hypothesis was determined based on a previous multicenter study of carvedilol results in a mean population Δlog (BNP) of 0.18. TRPV2 expression on peripheral blood mononuclear cell surface, cardiac events, total mortality, left ventricular fractional shortening, human atrial natriuretic peptide, cardiac troponin T, and creatine kinase, and pinch strength were also assessed.ResultsBecause of the poor general condition of many patients, only 18 of 34 patients were included and 13 patients could be treated according to the protocol throughout the 6-month period. However, there were no serious adverse events related to tranilast except diarrhea, a known adverse effect, and the drug was administered safely. TRPV2 expression on the mononuclear cell surface was elevated at baseline and reduced after treatment. Cardiac biomarkers such as BNP, human atrial natriuretic peptide, and fractional shortening remained stable, suggesting a protective effect against the progression of heart failure. In the per protocol set group, Δlog [BNP] was − 0.2 and significantly lower than that in the null hypothesis.ConclusionsTranilast is safe and effective in inhibiting TRPV2 expression, even in MD patients with advanced heart failure. Further trials are needed to evaluate the efficacy of tranilast in preventing myocardial damage, heart failure, motor impairment, and respiratory failure.Clinical trial registration The study was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000031965, URL: http://www.umin.ac.jp/ctr/) [March 30, 2018] and the Japan Registry of Clinical Trials (jRCT, registration number: jRCTs031180038, URL: https://jrct.niph.go.jp/) [November 12, 2021]. Patient registration was started in December 19, 2018.

Short-term outcomes in patients with non-ST-segment elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The proportion of non-ST-segment elevation myocardial infarction (NSTEMI) is increasing among the acute coronary syndromes (ACS). Reinfarction (RI) is a potential complication in high-risk patients with NSTEMI and it will cause an impact on these patients’ prognosis. Purpose Identify high-risk patients with RI and their prognosis in the setting of NSTEMI. Methods Based on a multicenter retrospective study, data collected from admissions between January 2013 and January 2020. Patients without data on previous cardiovascular history or uncompleted clinical data were excluded. Patients were divided in 2 groups (G): G1 – patients without RI; G2 - patients with RI during hospitalization. Logistic regression and survival analysis were performed. Results 7180 patients were admitted with NSTEMI, RI occurred in 71 pts (0.99%). Regarding epidemiological and past history G2 was older (71±12 vs 66±12, p=0.001), had higher rates of previous stroke (15.9% vs 7.0%, p 0.003) and peripheric arterial disease (6.3% vs 6.1%, p=0.004). The groups were similar regarding arterial hypertension (p=0.74), diabetes type 2 (p=0.11) and dyslipidaemia (p=0.48). G2 had higher levels of brain natriuretic peptide (45.5% vs 24.5%, p&amp;lt;0.001) and lower levels of haemoglobin (20.3% vs 7.9%, p&amp;lt;0.001). Patients taking prasugrel (2% vs 0.3%, p=0.002) or ticagrelor (6.1% vs 2.2%, p&amp;lt;0.001) previously to the admission were more susceptible to have RI. Patients with severe left ventricular systolic dysfunction (3.4% vs 2.6%, p&amp;lt;0.001), need of invasive (2.8% vs 0.8%, p&amp;lt;0.001) or non-invasive (4.2% vs 1.3%, p&amp;lt;0.001) ventilation and percutaneous coronary intervention (PCI) (80.3% vs 64.7%, p0.006) had higher rates of RI. Logist regression confirmed that PCI (p=0.03, OR 2.22, CI 1.08-4.53), previous stroke (p=0.02, OR 0.58, CI 0.37-0.92) and pts previously taking prasugrel (p=0.02, OR 1.85, CI 1.11-3.10) were predictors of RI in the setting of NSTEMI. Conclusion RI in the setting of NSTEMI was associated with PCI, previous stroke and pts previously taking prasugrel. One year prognosis was poorer for patients who suffered RI.

Brain natriuretic peptide levels are associated with cycle length average and are different between Ben-Dov and Corra exercise oscillatory ventilation definitions in heart failure patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CAPES e FAPERGS. Background The brain natriuretic peptide (BNP) is a marker of ventricular dysfunction related to severity and prognosis in heart failure patients. Exercise oscillatory ventilation (EOV) is a phenomenon in the ventilatory pattern associated with a worse prognosis in heart failure patients. EOV diagnosis is defined by the interaction among amplitude, cycle length, and the total time of the oscillations. Ben-Dov and Corrà definitions are used to identify EOV-positive cases by different criteria, which may stratify EOV patients with distinct clinical characteristics. Purpose To assess the BPN levels in heart failure patients and to test BNP level correlation with amplitude, cycle length, and total oscillation time according to Ben-Dov and Corrà definitions. Methods Data from 242 cardiopulmonary exercise tests (CPETs) performed between 2011 and 2014 at an Italian heart centre were screened for EOV identification. CPETs were done in a cycle-ergometer with gas exchange analysed breath-by-breath. EOV cases were identified according to the definitions of Ben-Dov and Corrà. Mann-Whitney test was applied to compare BPN levels between the EOV-positive and negative in each definition and between EOV-positive from Ben-Dov and Corrà definitions. Spearman coefficient (rs) evaluated the association between amplitude and length average of the oscillatory cycle, percentage of total oscillation time, and BNP levels in each EOV definition. The BNP levels from EOV-positive identified by Corrà or Ben-Dov definition alone, and from patients who have met the criteria of both definitions were compared by the Kruskal-Wallis test. Results Sixty-seven patients were identified as EOV-positive. From them, 19 were identified exclusively by the Ben-Dov and 26 by Corrà. Twenty-two met the criteria for both definitions. Overall, no difference in EOV prevalence between Ben-Dov and Corrà definitions was found (20.4 vs 24.2%, p = 0.482). EOV-positive identified by the Ben-Dov definition have higher BNP levels than EOV-negative (p &amp;lt; 0.01) and the EOV-positive by Corrà definition (p = 0.025) (Table 1). Spearman correlation showed association just between BNP levels and cycle length average from EOV-positive by the Ben-Dov (rs = 0.566; p &amp;lt; 0.001) and by Corrà (rs = 0.339; p = 0.011) (Figure 1). When analysed by exclusive criteria identification, the BNP levels were higher in EOV-positive identified by Ben-Dov than Corrà (737 [562 to 1,178] vs 276 [221 to 603] pg/mL; p = 0.009). BNP levels in the EOV-positive identified by both definitions (475 [347 to 852] pg/mL) were not different from those identified by the Ben-Dov and Corrà definitions alone. Conclusion EOV-positive identified by the Ben-Dov have higher BNP levels than EOV-negative and the EOV-positive identified by Corrà, alone or not. BNP levels also are associated with the cycle length average, with a higher correlation for the Ben-Dov EOV-positive.

The Utility of Brain Natriuretic Peptide in Patients Undergoing an Initial Evaluation for Pulmonary Hypertension.

IntroductionBrain natriuretic peptide (BNP) is a polypeptide released from the cardiac ventricles and has been used as a diagnostic marker in cardiovascular diseases. Some patients with pulmonary hypertension have significant increases in BNP levels. This study wanted to determine whether the BNP levels in patients referred for evaluation of possible pulmonary hypertension were associated with a particular functional class or diagnostic group.MethodsData were collected on patients from the Pulmonary Vascular Disease clinic undergoing right heart catheterization between 1/1/2019 and 5/20/2020. Clinical information, laboratory results including BNP, and hemodynamic parameters were recorded.ResultsThis study included 117 patients referred for evaluation for PH with measured BNP levels. The mean age was 63; the female to male ratio was 2:1, 25.4% of the patients were Hispanic. The average BNP level for the entire cohort was 4127.1 ± 11761.98 pg/ml. Patients in higher WHO functional classes tended to have higher levels of BNP, but statistical analysis BNP showed no differences between the functional classes. Patients in WHO Group 4 had significantly higher BNP levels than other WHO groups. Hemodynamic group classification demonstrated significant differences in BNP values between the low, intermediate, and high composite score patients.ConclusionsPatients undergoing evaluation for pulmonary hypertension had a wide range of BNP values. Patients with more abnormal composite hemodynamic scores higher BNP levels. Measurement of BNP provides an independent test to help interpret patients’ descriptions of their functional limitations and to identify patients with more abnormal hemodynamic parameters.

Short-term outcomes in patients with non-ST-segment elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The proportion of non-ST-segment elevation myocardial infarction (NSTEMI) is increasing among the acute coronary syndromes (ACS). Reinfarction (RI) is a potential complication in high-risk patients with NSTEMI and it will cause an impact on these patients’ prognosis. Purpose Identify high-risk patients with RI and their prognosis in the setting of NSTEMI. Methods Based on a multicenter retrospective study, data collected from admissions between January 2013 and January 2020. Patients without data on previous cardiovascular history or uncompleted clinical data were excluded. Patients were divided in 2 groups (G): G1 – patients without RI; G2 - patients with RI during hospitalization. Logistic regression and survival analysis were performed. Results 7180 patients were admitted with NSTEMI, RI occurred in 71 pts (0.99%). Regarding epidemiological and past history G2 was older (71±12 vs 66±12, p=0.001), had higher rates of previous stroke (15.9% vs 7.0%, p 0.003) and peripheric arterial disease (6.3% vs 6.1%, p=0.004). The groups were similar regarding arterial hypertension (p=0.74), diabetes type 2 (p=0.11) and dyslipidaemia (p=0.48). G2 had higher levels of brain natriuretic peptide (45.5% vs 24.5%, p&amp;lt;0.001) and lower levels of haemoglobin (20.3% vs 7.9%, p&amp;lt;0.001). Patients taking prasugrel (2% vs 0.3%, p=0.002) or ticagrelor (6.1% vs 2.2%, p&amp;lt;0.001) previously to the admission were more susceptible to have RI. Patients with severe left ventricular systolic dysfunction (3.4% vs 2.6%, p&amp;lt;0.001), need of invasive (2.8% vs 0.8%, p&amp;lt;0.001) or non-invasive (4.2% vs 1.3%, p&amp;lt;0.001) ventilation and percutaneous coronary intervention (PCI) (80.3% vs 64.7%, p0.006) had higher rates of RI. Logist regression confirmed that PCI (p=0.03, OR 2.22, CI 1.08-4.53), previous stroke (p=0.02, OR 0.58, CI 0.37-0.92) and pts previously taking prasugrel (p=0.02, OR 1.85, CI 1.11-3.10) were predictors of RI in the setting of NSTEMI. Conclusion RI in the setting of NSTEMI was associated with PCI, previous stroke and pts previously taking prasugrel. One year prognosis was poorer for patients who suffered RI.