Brain Natriuretic Peptide Concentrations Research Articles

P26.06 High frequency of Fatal Immune Checkpoint Inhibitor Associated Myocarditis in B2/B3 Thymoma Patients

Myocarditis, the incidence was around 0.09%, is uncommon adverse event of immune checkpoint inhibitors (ICI), but is often serious with a relatively high mortality. However, the incidence of myocarditis was reported much higher in thymic epithelial tumor patients treated with immunotherapy, which was 5%-9%. Myocarditis after ICI in thymic epithelial tumor has not been well characterized. We retrospectively analyzed patients diagnosed with myocarditis after ICI in thymic epithelial tumor in our hospital from January 2016 to July 2019. The main outcomes were clinical manifestations. We also searched on Pubmed database up until 03/13/2020 with the following search terms: myocarditis, thymoma, checkpoint, or check point. Case reports on myocarditis caused by immune checkpoint inhibitors were selected. There were 301 patient diagnosed with thymic epithelial tumor in our hospital from January 2016 to July 2019. Eight patients treated with immune checkpoint inhibitors were included. Four patients developed myocarditis during pembrolizumab treatment, 1 patient during sintilimab. Median age was 48 (range 27-56) years. Two of them were male. Median time of onset of myocarditis was 12 days after starting ICI treatment (range 8-63 days). All of them were B1/B2/B3 thymoma subtype. In all patients, the concentrations of brain natriuretic peptide (BNP) and troponin increased obviously. Three of them died within 11 days after developed myocarditis. All of these 3 patients, troponin was more than 6000pg/ml and electrocardiogram showed ventricular arrhythmia. Only 1 patient had response to high-dose steroid treatment. Seven cases citing myocarditis as a side effect of ICI treatment in thymic epithelial tumor patients were identified by searching on Pubmed. All of them were B2/B3 thymoma subtype. Six of them received pembrolizumab treatment, and 1 patient received Nivolumab. Myocarditis occurred just after first dose of ICI therapy in 4 patients. The other two patients were developed myocarditis on the second cycle. Myocarditis may be more common than appreciated in B2/B3 thymoma patients treated with ICI treatment, especially with pembrolizumab, and it occurs early after starting ICI treatment. Further researches should be established in dealing or predicting with this potentially fatal side effect.

Speckle-tracking echocardiography in the early diagnosis of heart failure after ST-segment elevation myocardial infarction

Aim . To study the potential of global strain analysis using two-dimensional speckletracking echocardiography to predict the heart failure (HF) in patients with ST-segment elevation myocardial infarction (STEMI) based on the 6-month follow-up after revascularization. Material and methods . The study included 114 STEMI patients aged 52 (44; 59) years. Two-dimensional echocardiography was performed with analysis of standard parameters and speckle tracking with analysis of strain and rotational characteristics of the myocardium. Concentration of brain natriuretic peptide was determined. The endpoint was the presence of heart failure (HF) after 6-month follow-up. observation. The analysis of HF risk was carried out using ROC-curves based on 3 criteria. Strain parameters with the maximum sum of sensitivity and specificity were chosen as a cutoff point. Results . Six months after STEMI, depending on the ejection fraction (EF) value, the patients were divided into 3 groups: group 1 — patients with reduced EF (<40%) (HFrEF); group 2 — with mid-range EF (40-49%) (HfmrEF); group 3 — with preserved EF ≥50% (HFpEF). Strain and rotational characteristics differed between groups (p<0,001 for all). It was found that in the acute period of myocardial infarction, global longitudinal strain (GLS) <9,5% (AUR =0,804, 95% (confidence interval (CI) (0,673; 0,936), p=0,001) and global circumferential strain (GCS) <8,7% (AUR =0,722 (95% CI (0,568; 0,875), p=0,012) predicts the development of HFrEF. These values less than 12,5% (AUR =0,830 (95% CI (0,749; 0,911), p=0,001) and 13% (AUR =0,759 (95% CI (0,664; 0,855), p=0,001) is associated with HFmrEF The Twist had the highest predictive value in relation to HFrEF — 4,2° (AUR =0,998 (95% CI (0,993; 0,100), p=0,001). Conclusion . GLS, GCS and Twist have high sensitivity and specificity and can be used in wide clinical practice as simple and cost-effective indicators of HF risk.

Correlations between clinical and laboratory findings and prognostically unfavorable CMR-based characteristics of acute ST-elevation myocardial infarction.

Aim To evaluate factors associated with unfavorable predictive characteristics of ST-segment elevation acute myocardial infarction (STEMI) as per data of magnetic resonance imaging (MRI).Material and methods The study included 52 patients with STEMI who underwent a primary percutaneous coronary intervention (pPCI). Contrast-enhanced cardiac MRI was performed for all patients on days 3-7. Delayed contrast-enhancement images were used for assessing infarct size, presence of microvascular obstruction (MVO) areas, and heterogeneity zones.Results Multifactorial analysis showed that independent predictors of MVO were type 2 diabetes mellitus (DM) (relative risk (RR) 1.9, confidence interval (CI): 1.1-3.26, р=0.012), increased levels of brain natriuretic peptide (BNP) (RR 2.04, CI: 1.39-2.99, р=0.004) and creatine kinase (CK) (RR 2.06, CI: 0.52-0.80, р=0.02), and infarct size (IS) (RR 2.81; CI: 1.38-5.72, р=0.0004). Construction of ROC curves provided the quantitative values of study indexes, at which the risk of MVO increased. For BNP, this value was ≥276 pg/ml (sensitivity, 95.7 %; specificity, 37.9 %); for CK ≥160 U/l (sensitivity, 74.1 %; specificity, 61.9 %); and for IS ≥18.8 % (sensitivity, 79.3 %; specificity, 69.6 %). Correlation analysis of risk factors for increased size of the heterogeneity zone showed significant correlations of the heterogeneity zone size with older age of patients (r=0.544, р<0.0001), higher concentrations of BNP (r=0.612, р<0.0001), CK (r=0.3, 95 % CI: 0.02-0.5, р=0.03), and C-reactive protein (CRP) (r=0.59, CI: 0.3-0.7, р=0.0001). Increased levels of CK (r=0.53, 95 % CI: 0.29-0.70, р=0.0001) and BNP (r=0.55, 95 % CI: 0.28-0.70, p=0.0003) significantly correlated with increased IS.Conclusion Risk of MVO formation as per MRI data increased in the presence of type 2 DM and IS ≥18.8 % (р<0.05). Formation of MVO in patients with STEMI was associated with increased levels of BNP ≥276 pg/ml and CK ≥160 U/l (р<0.05). Increased levels of BNP, CK, and CRP were associated with a larger size of heterogeneity zone according to data of the correlation analysis. A larger heterogeneity zone was more typical for older patients. Increased levels of CK and BNP were also associated with larger IS. The correlation analysis did not show any significant interactions between the size of heterogeneity zone, IS, and MVO size (р>0.05).

Cardiac troponin I and BNP for predicting zero Agatston score in patients with diabetes mellitus

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Coronary artery calcifications (CAC) scoring assessed by the Agatston score has shown an excellent prognostic value in large studies, particularly in diabetic patients, with a very low rate of cardiovascular events in patients with a zero Agatston score. Moreover, recent studies have suggested that high-sensitive cardiac troponin I (hs-cTnI) and brain natriuretic peptide (BNP) may be useful for detecting subclinical atherosclerosis, especially in diabetic patients. However, the link between hs-cTnI/BNP and the Agatston score has not been investigated in this population. PURPOSE The aim of this study was to investigate if hs-cTnI and BNP can bring additional value to predict zero Agatston score in patients with diabetes mellitus in addition to usual risk factors. METHODS Between 2015 and 2019, CAC score was prospectively performed in consecutive patients with diabetes mellitus with high cardiovascular risk. Patients with symptoms or known coronary artery disease were excluded. Within 24h from CT exam, peripheral blood samples were taken to measure hs-cTnI and BNP. The relationship between serum hs-cTnI/BNP concentrations and zero Agatston score was evaluated using univariate and multivariate binomial models. 77 variables have been used to build the model. The implication of hs-cTnI and BNP in this multivariate model was evaluated using nested models associated with Chi-squared test of independence. RESULTS A total of 844 patients with diabetes were enrolled (61 ± 7 years, 57% men, mean diabetes duration 18 years). In this population, 294 (35%) had a zero Agatston score, 253 (30%) an Agatston score from 1 to 100, 161 (19%) from 101 to 400, and 136 (16%) higher than 400. In univariate analysis, hs-cTnI and BNP concentrations were associated with a zero Agatston score (respectively OR, 2.63 [95% CI, 1.51-5.01]; p < 0.001 and OR, 1.09 [95% CI, 1.01-1.22]; p = 0.03). In multivariate analysis, hs-cTnI and BNP concentrations were associated with a zero Agatston score (respectively OR, 2.38 [95% CI, 1.51-4.76]; p = 0.009 and OR, 1.18 [95% CI, 1.07-1.32]; p = 0.001). Among the 77 variables, the multivariate model including age, gender, smoking, dyslipidaemia, duration of the diabetes, arterial hypertension, presence of diabetic neuropathy, hs-cTnI and BNP concentrations, significantly discriminated the zero Agatston score (AUC = 0.81; p < 0.001). The most discriminant threshold was ≤ 3ng/l for hs-cTnI and <17ng/l for BNP. In nested models, both hs-cTnI and BNP brought information to this multivariate model to predict a zero Agatston score (respectively p = 0.003 and p < 0.001 to the Chi-squared test). Moreover, removing hs-cTnI and BNP from the model results in a significant reduction in model performance (AUC = 0.79; p = 0.004). CONCLUSIONS Cardiac biomarkers hs-cTnI and BNP are associated with a zero Agatston score, which is correlated with a very low risk of cardiovascular events in asymptomatic patients with diabetes mellitus. Abstract Figure. ROC curve to predict zero Agatston score

Preoperative heart failure is not associated with impaired coagulation in paediatric cardiac surgery.

The objectives of the present study were to determine whether there was any association between the grade of heart failure, as expressed by preoperative levels of brain natriuretic peptide and Ross score, and the preoperative coagulation status in patients with non-restrictive ventricular shunts and determine whether there were any postoperative disturbances of the coagulation system in these patients, as measured by thromboelastometry and standard laboratory analyses of coagulation. Perioperative coagulation was analysed with laboratory-based coagulation tests and thromboelastometry before, 8 hours after, and 18 hours after cardiac surgery. In addition, brain natriuretic peptide was analysed before and 18 hours after surgery. 40 children less than 12 months old with non-restrictive congenital ventricular or atrio-ventricular shunts scheduled for elective repair of their heart defects. All coagulation parameters measured were within normal ranges preoperatively. There was a significant correlation between brain natriuretic peptide and plasma fibrinogen concentration preoperatively. There was no statistically significant correlation between brain natriuretic peptide and INTEM-MCF, FIBTEM-MCF, plasma fibrinogen, activated partial thromboplastin time, prothrombin time, or platelet count at any other time point, either preoperatively or postoperatively. Postoperatively, fibrinogen plasma concentration and FIBTEM-MCF decreased significantly at 8 hours, followed by a large increase at 18 hours to higher levels than preoperatively. There was no evidence of children with non-restrictive shunts having coagulation abnormalities before cardiac surgery. Brain natriuretic peptide levels or Ross score did not correlate with coagulation parameters in any clinically significant way.

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

PurposeMyocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure.MethodsVolume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls.ResultsIn ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls.ConclusionOpioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.

Cardiac Troponin I and BNP for Predicting Zero Agatston Score in Patients with Diabetes Mellitus

Coronary artery calcifications (CAC) scoring assessed by the Agatston score has shown an excellent prognostic value in large studies and particularly in diabetic patients, with a very low rate of cardiovascular events in patients with a zero Agatston score. Moreover, recent studies have suggested that high-sensitive cardiac troponin I (hs-cTnI) and brain natriuretic peptide (BNP) may be useful for detecting subclinical atherosclerosis. However, the link between hs-cTnI/BNP and the Agatston score has not been investigated in patients with diabetes. The aim of this study was to investigate if hs-cTnI and BNP can bring additional value to predict zero Agatston score in patients with diabetes mellitus in addition to usual risk factors. Between 2015 and 2019, CAC score was prospectively performed in consecutive patients with diabetes mellitus. Patients with symptoms, known coronary artery disease or history of atrial fibrillation were excluded. Within 24 h from CT examination, peripheral blood samples were taken to measure hs-cTnI and BNP. The relationship between serum hs-cTnI/BNP concentrations and zero Agatston score was assessed using univariate and multivariate binomial models. The implication of hs-cTnI and BNP in this multivariate model was evaluated using nested models associated with Chi 2 test of independence. A total of 844 patients with diabetes were enrolled (61 ± 7years, 57% men, mean duration of diabetes 18years). In this population, 294(35%) had a zero Agatston score, 253(30%) an Agatston score from 1 to 100, 161(19%) from 101 to 400, and 136(16%) higher than 400. In univariate analysis, hs-cTnI and BNP concentrations were associated with zero Agatston score (respectively OR, 2.63 [95%CI, 1.51-5.01]; P < 0.001 and OR, 1.09 [95%CI, 1.01-1.22]; P = 0.03). In multivariate analysis, hs-cTnI and BNP concentrations were associated with zero Agatston score (respectively OR, 2.38 [95%CI, 1.51-4.76]; P = 0.009 and OR, 1.18 [95%CI, 1.07-1.32]; P = 0.001). The multivariate model included age, gender, smoking, dyslipidemia, duration of diabetes, hypertension, diabetic neuropathy, hs-cTnI and BNP concentrations, significantly discriminated the zero Agatston score (AUC = 0.81; P < 0.001) ( Fig. 1 ). The most discriminant threshold was ≤ 3 ng/l for hs-cTnI and < 17 ng/l for BNP. In nested models, both hs-cTnI and BNP brought information to this multivariate model to predict a zero Agatston score (respectively P = 0.003 and P < 0.001). Moreover, removing hs-cTnI and BNP from the model results in a significant reduction in model performance (AUC = 0.79; P = 0.004). Cardiac biomarkers hs-cTnI and BNP are associated with zero Agatston score, which is correlated with a very low risk of cardiovascular events, in asymptomatic patients with diabetes mellitus.

Echocardiographic follow-up to right ventricular modifications in secondary pulmonary hypertension to diabetes in rats

ABSTRACT Clinical studies suggest that diabetes is a risk factor in the development of pulmonary arterial hypertension. The increase in blood pressure in the pulmonary area is characterized by the increase in the afterload and hypertrophy of the right ventricle. The objective of this study was to conduct a longitudinal follow-up of the morphological and functional changes in the right ventricle in a rat model with pulmonary arterial hypertension secondary to diabetes. Male Sprague Dawley rats were randomly divided into a control group (saline solution) and a diabetic group (60 mg/kg with streptozotocin). For 12 weeks, an echocardiography for longitudinal (in vivo) image analysis of the pulmonary pressure was performed at the same time as the evaluation of myocardial remodeling and right ventricular. After this period, the pulmonary pressure was measured by means of a pulmonary artery catheterization, and the presence of hypertrophy was determined by means of the Fulton index. The plasma concentration of brain natriuretic peptide was measured by means of the ELISA technique. It was found that the diabetic rats showed an increase in pressure in the pulmonary arteries, an increase in the Fulton index, and an increase in brain natriuretic peptide. The echocardiographic follow-up showed that the diabetic rats presented an increase in the pulmonary artery from the fourth week, while hypertrophy and right ventricular systolic dysfunction occurred until the twelfth week. In conclusion, pulmonary arterial hypertension induced by experimental diabetes generated hypertrophy and systolic dysfunction of the right ventricle.

Early Predictors of Heart Failure Progression in Patients After Myocardial Infarction.

Aim To identify early predictors for progression of chronic heart failure (CHF) in patients with ST-segment elevation myocardial infarction (STEMI).Material and methods The study included 113 patients with STEMI aged 52 (95 % confidence interval, 36 to 65) years. 24-h ECG monitoring was performed with assessment of ventricular late potentials, QT dispersion, heart rhythm turbulence (HRT), and heart rhythm variability (HRV); XStrain 2D echocardiograpy with determination of volumetric parameters, myocardial strain characteristics and velocities; and measurement of brain natriuretic peptide (BNP) concentrations. The endpoint was CHF progression during 48 weeks of follow-up, which was observed in 26 (23 %) patients. Based on the outcome, two groups were isolated, with CHF progression (Prg) (26(23%)) and with a relatively stable CHF postinfarction course (Stb) (87 (77 %)).Results At 12 weeks following MI, the Prg group showed increases in left ventricular (LV) end-diastolic dimension (EDD) (р&lt;0.05) and end-diastolic and end-systolic volumes (EDV, ESV), (р&lt;0.01), and EDV and ESV indexes (EDVi and ESVi, р&lt;0.01). In this group, global longitudinal strain (GLS) was decreased at 24 weeks (р&lt;0.05) and global radial strain (GRS) was decreased at 48 weeks (р=0.0003). In the Prg group, values of strain parameters (GLS, global circular strain (GCS), and GRS) were lower at all times. At 7-9 days, 24 weeks, and 48 weeks, the proportion of patients with pathological HRT was higher in the Prg group (38, 27, and 19 % for the Prg group vs 14 % (р=0.006); 3,4 % (р=0.001), and 2.3 % (р=0.002) for the Stb group, respectively). Only in the Stb group, increases in HRV were observed (SDNNi by 13 % (р=0.001), rMSSD by 24 % (р=0.0002), TotP by 49 % (р=0.00002), VLfP by 23 % (р=0.003), LfP by 22 % (р=0.008), and HfP by 77 % (р=0.002). At 7-9 days of MI, the Stb group had greater values of SDANN (р=0.013) and HfP (р=0.01). CHF progression correlated with abnormal values of turbulence onset (TO), disturbed HRT, increased BNP levels and LV ESD, and low values of GLS, GCS, and GRS. Combined assessment of HRT, LV ESD, and GLS at 7-9 days after STEMI allows identifying patients with high risk for CHF progression in the next 48 weeks.Conclusion The markers for CHF progression after STEMI include abnormal TO values, disturbed HRT, increased BNP levels and LV ESD, and low values of GLS, GCS, and GRS. The multifactor logistic regression analysis revealed early predictors of CHF in the postinfarction period, including abnormal TO, increased LV ESD, and reduced GLS.

Influence of Omega-3 PUFA on Non-invasive factors determining the risk of arrhYthmias eXcess and sudden cardiac death in patients with HFpEF with ischemic etiology (ONYX)

Aim Patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) who have had acute myocardial infarction have an unfavorable prognosis, largely due to ventricular arrhythmias (VA) and risk of sudden cardiac death (SCD). The optimal treatment (triple neurohormonal blockade plus implantable cardioverter defibrillator and cardiac resynchronization therapy) reduced the risk of SCD primarily due to reverse cardiac remodeling, but has not solved this problem completely. Efficacy of purified ω-3 polyunsaturated fatty acid esters (PUFA) in low doses (1 g/day) in reducing VA and risk of SCD in HFrEF patients was demonstrated in two large randomized clinical trials. The PUFA effects was suggested to be related also with increased heart rhythm variability (HRV) and chronotropic action, which might depend on the drug dose. The present open, prospective, randomized, comparative study in parallel groups evaluated the effect of Omacor in different doses on noninvasive markers of SCD risk in patients with ischemic HFrEF receiving the optimal drug therapy.Methods Patients (n=40) were randomized at a 1:1:2 ratio to the control group (n=10), the Omacor 1 g/day treatment group (n=10), and the Omacor 2 g/day treatment group (n=20) and were followed up for 12 months. Clinical evaluation included changes in the CHF functional class (FC) and Clinical Condition Scale (CCS) score; concentration of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP); and peak oxygen consumption during exercise (peak VO2). The LV function was evaluated by LVEF. Holter ECG monitoring was used for evaluation of HRV (SDNN), average 24-h heart rate (HR), number of ventricular extrasystoles (VE) per hour and severity of VA, and presence of paired VE and VT runs.Results Improvement of CHF FC became significant only with the high-dose Omacor treatment (2 g/day). The CCS score showed a tendency towards decrease also with a lower dose (1 g/day) whereas the level of NT-proBNP significantly decreased with both Omacor doses. The increase in LV EF was significant only with the use of Omacor 2 g/day (+3 %, р=0.002). A negative chronotropic effect of ω-3 PUFA was observed. Average 24-h HR decreased by 8 bpm (р=0.05) and 11 bpm (р&lt;0.001) with Omacor 1 g/day and 2 g/day, respectively. Either dose of ω-3 PUFA significantly improved VO2, which directly correlated with LV EF and inversely correlated with HR. The decrease in number of VE was associated not only with improved HRV (SDNN) but also with the decrease in 24-h HR, and thus Omacor 2 g/day significantly decreased the number of VE (by 16 per hour) and dangerous VA (paired VE and VT runs ceased to be detected in 40 % of patients).Conclusion Since HR, HRV, and VA are closely interrelated, the effect of ω-3 PUFA specifically on these noninvasive markers apparently determines its ability to decrease the risk of SCD in patients with ischemic HFrEF. The antiarrhythmic effect of Omacor was greater with higher doses of this drug.

Cardiac troponin I and BNP for predicting zero Agatston score in patients with diabetes mellitus

Abstract Background Coronary artery calcifications (CAC) scoring assessed by the Agatston score has shown an excellent prognostic value in large studies, particularly in diabetic patients, with a very low rate of cardiovascular events in patients with a zero Agatston score. Moreover, recent studies have suggested that high-sensitive cardiac troponin I (hs-cTnI) and brain natriuretic peptide (BNP) may be useful for detecting subclinical atherosclerosis, especially in diabetic patients. However, the link between hs-cTnI/BNP and the Agatston score has not been investigated in this population. Purpose The aim of this study was to investigate if hs-cTnI and BNP can bring additional value to predict zero Agatston score in patients with diabetes mellitus in addition to usual risk factors. Material Between 2015 and 2019, CAC score was prospectively performed in consecutive patients with diabetes mellitus with high cardiovascular risk. Patients with symptoms or known coronary artery disease were excluded. Within 24h from CT exam, peripheral blood samples were taken to measure hs-cTnI and BNP. The relationship between serum hs-cTnI/BNP concentrations and zero Agatston score was evaluated using univariate and multivariate binomial models. 77 variables have been used to build the model. The implication of hs-cTnI and BNP in this multivariate model was evaluated using nested models associated with Chi-squared test of independence. Results A total of 844 patients with diabetes were enrolled (61±7 years, 57% men, mean diabetes duration 18 years). In this population, 294 (35%) had a zero Agatston score, 253 (30%) an Agatston score from 1 to 100, 161 (19%) from 101 to 400, and 136 (16%) higher than 400. In univariate analysis, hs-cTnI and BNP concentrations were associated with a zero Agatston score (respectively OR, 2.63 [95% CI, 1.51–5.01]; p&amp;lt;0.001 and OR, 1.09 [95% CI, 1.01–1.22]; p=0.03). In multivariate analysis, hs-cTnI and BNP concentrations were associated with a zero Agatston score (respectively OR, 2.38 [95% CI, 1.51–4.76]; p=0.009 and OR, 1.18 [95% CI, 1.07–1.32]; p=0.001). Among the 77 variables, the multivariate model including age, gender, smoking, dyslipidaemia, duration of the diabetes, arterial hypertension, presence of diabetic neuropathy, hs-cTnI and BNP concentrations, significantly discriminated the zero Agatston score (AUC = 0.81; p&amp;lt;0.001). The most discriminant threshold was ≤3ng/l for hs-cTnI and &amp;lt;17ng/l for BNP. In nested models, both hs-cTnI and BNP brought information to this multivariate model to predict a zero Agatston score (respectively p=0.003 and p&amp;lt;0.001 to the Chi-squared test). Moreover, removing hs-cTnI and BNP from the model results in a significant reduction in model performance (AUC = 0.79; p=0.004). Conclusions Cardiac biomarkers hs-cTnI and BNP are associated with a zero Agatston score, which is correlated with a very low risk of cardiovascular events in asymptomatic patients with diabetes mellitus. ROC curve to predict zero Agatston score Funding Acknowledgement Type of funding source: None

Biomarkers associated with poor prognosis in patients with end-stage heart failure

Abstract Background Despite advances in the treatment, end-stage heart failure (HF) is a disease with a severe prognosis, showing an annual mortality rate of 30 to 50%. Due to a poor prognosis in this population of patients, it is necessary to accurately stratify the risk of death, including simple and effective prognostic markers. Objective This study aimed to determine biomarkers associated with mortality in patients with end-stage HF. Material and methods The study was a prospective analysis of optimally treated patients with end-stage HF, who were hospitalised at the Cardiology Department between 2016 and 2018. At the time of enrollment to the study routine laboratory tests, cardiopulmonary exercise tests, echocardiography and right heart catheterization were performed in all patients. Human Interleukin 33 (IL-33) and IL-1 Receptor Like 1 (IL1RL1) were measured by sandwich enzyme-linked immunosorbent assay (ELISA) with the commercially available kit (Human Il-33 and IL1RL1 ELISA kit, SunRedBio Technology Co, Ltd, Shanghai, China). Plasma concentration of N-terminal brain natriuretic peptide (NT-proBNP) was measured using a commercially available kit (Human NTproBNP ELISA kit, Roche Diagnostics, Mannheim, Germany). The endpoint was all-cause mortality during a one-year follow-up. The Medical University of Silesia's local Institutional Review Board approved the study protocol, and all patients provided informed consent. Results The final study group consisted of 282 patients (87.6% males, median age 57.0 years). One-year mortality rate in the analysed population was 28%. In a multivariate analysis, independent risk factors of death included NT-proBNP [Hazard Ratio (HR) 1.056 (95% Confidence Interval (CI): 1.024–1.089); P&amp;lt;0.001], sodium [HR 0.877 (95% CI: 0.815–0.944); p&amp;lt;0.001], IL33 [HR 0.977 (95% CI: 0.965- 0.989); p&amp;lt;0.001] and IL1RL1 [HR 1.015 (95% CI: 1.008–1.023); p&amp;lt;0.001) serum levels. Conclusions Our study showed that lower sodium and IL-33 levels, as well as higher NT-proBNP and IL1RL1 levels are associated with an increased risk of death in patients with end-stage HF during a one-year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, Poland

Experimental model of congestive heart failure induced by transverse aortic constriction in BALB/c mice

IntroductionMurine transverse aortic constriction (TAC) is a frequently used model of pressure overload-induced left ventricular (LV) remodeling. However, there is considerable variability in disease progression to overt heart failure (HF) development in the most commonly used strain of mice (i.e., C57BL/6J). Studies have shown that C57BL/6J mice are more resistant than BALB/c mice to congestive HF development following myocardial infarction or angiotensin II-induced hypertension. Therefore, we tested the hypothesis that BALB/c mice may be a better research model to study TAC-induced progressive HF. MethodsFollowing sham or TAC surgery in both C57BL/6J (n = 29) and BALB/c (n = 32) mice, we evaluated cardiac dimensions and function by echocardiography at 2, 4, 8, and 12 weeks and monitored survival throughout the study. In a separate cohort of BALB/c mice, we repeated the study in the presence of the angiotensin converting enzyme inhibitor enalapril or a vehicle initiated 2 weeks post-TAC and administered for 6 weeks. At the end of the studies, we assessed the heart weight, lung weight, and plasma brain natriuretic peptide (BNP) concentration. ResultsFollowing comparable TAC, both C57BL/6J and BALB/c mice showed significant LV remodeling compared with the sham control mice. BALB/c mice progressively developed systolic dysfunction, LV dilation, lung congestion, and significant mortality, whereas C57BL/6J mice did not. In the separate cohort of BALB/c TAC mice, enalapril significantly reduced the heart weight, lung weight, and plasma BNP concentration and improved survival compared with the vehicle control. DiscussionBALB/c mice uniformly developed congestive HF post-TAC. Enalapril was effective in improving survival and reducing lung congestion in this model. The data suggest that BALB/c mice may be a better research tool than C57BL/6J mice to study TAC-induced disease progression to HF and to evaluate novel therapies for the treatment of chronic HF with reduced ejection fraction.

The diagnostic value of brain natriuretic peptide in men with comorbid essential arterial hypertension and type 2 diabetes mellitus

The aim of the work is to investigate the diagnostic informativeness of brain natriuretic peptide (BNP) in men with left ventricular (LV) diastolic dysfunction (DD) and initial stages of chronic heart failure (CHF) in comorbid stage 2 essential hypertension (EH 2) and type 2 diabetes mellitus (T2DM).Materials and methods. We examined 211 men. 79 people without signs of cardiovascular disease were assigned to a control group. 62 patients with EH 2 and CHF no higher than NYHA functional class (FC) I were included in the 1st, and 70 men with EH 2 combined with T2DM and CHF FC I–II formed the 2nd main study group. The plasma concentration of BNP was measured by ELISA. The examination included the determination of HbA1c, blood lipid profile, echocardiography. The mathematical processing was performed using the standard statistical package Statistica 6.1.Results. Plasma levels of BNP in comorbid EH 2 and T2DM were significantly higher (102.18 ± 4.18 pg/ml) than those in patients with EH without T2DM (77.40 ± 2.85 pg/ml) and in subjects without cardiovascular diseases (21.74 ± 0.59 pg/ml) (P &lt; 0.00001). According to the regression analysis, the level of BNP was associated with changes in parameters of intracardiac hemodynamics in patients with EH2. In patients with comorbid EH 2 and T2DM, the level of BNP was also associated with indicators of systemic hemodynamics and body weight. BNP as a marker of CHF at the recommended borderline level (35 pg/ml) in patients with EH 2 and T2DM was characterized by a sensitivity of 98.57 % and specificity of 55.32 %. The BNP borderline levels with higher specificity were determined for early diagnosis of CHF in EH 2 with T2DM and obesity comorbidities.Conclusions. BNP, as an early marker of LV DD and the initial stages of CHF at the recommended borderline level in men with comorbid EH 2 and T2DM does not have sufficiently high specificity. In these pathological conditions, the determined borderline levels of BNP can be used as indicative surrogate markers for early diagnosis of CHF during screening with the view to identify persons for further echocardiographic additional examination and in cases where echocardiography is not possible.

The role of the brain natriuretic peptide gene polymorphism in the diagnostic use of the biomarker in myocardial dysfunction in men, residents of Podillya with comorbid essential hypertension and type 2 diabetes mellitus

There is a growing interest in the early detection of signs of myocardial dysfunction, especially in comorbid patients for timely prevention of progression of disease, reducing the risk of complications, improving their quality of life. The aim of the work was to optimize the diagnosis of myocardial dysfunction in men, residents of Podillya, taking into account the plasma concentration of brain natriuretic peptide (BNP) and polymorphism of the corresponding gene under conditions of comorbidity of essential hypertension (EH) with left ventricular hypertrophy (LVH) and type 2 diabetes mellitus (T2D). We examined 211 men: 79 persons without the signs of cardiovascular diseases, 62 patients with EH 2 and chronic heart failure (CHF) 0-I functional classes (FC) according to NYHA Classification and 70 – with EH 2 combined with T2D and CHF FC I-II. The examination included the determination of plasma concentration of BNP, the brain natriuretic peptide gene polymorphism (polymorphic locus T-381C), indices of doppler-echocardiography. The mathematical processing was performed using the standard statistical package Statistica 10. During the study, we calculated the primary statistical indicators, identified differences between groups on statistical grounds, made correlation and discriminant analysis. Diastolic dysfunction (DD) of the left ventricle (LV) was diagnosed in 45.16% of patients in the group with EH 2, and 90% in the group of comorbid patients. It was determined that men, residents of Podillya, with presence and absence of T2D, have dominating T381C genotype of the BNP gene (p&gt;0.05). Lower plasma concentration of BNP that is peculiar for homozygous T381T genotype, in comparison with carriers of allele C of BNP gene and the average values of this biomarker in patients with DD may affect its informativeness in the diagnosis of myocardial dysfunction and requires a lower level of diagnosis. Appropriate borderline levels of BNP were determined for early diagnosis of DD in carriers of polymorphic variants of the BNP gene in men, residents of Podillya, with comorbid course of EH 2 and T2D. It is recommended to determine the genotype of the corresponding gene (polymorphic locus T-381C) and plasma level of BNP and focus on the calculated borderline levels of BNP to optimize the diagnosis of myocardial dysfunction in comorbid patients with EH 2 and T2D. For carriers of the T381T genotype it is ≥55.57 pg/ml, for carriers of the C allele (heterozygous T381C and homozygous C381C) of the BNP gene it is ≥69.13 pg/ml.

Systemic-to-Pulmonary Collateral Flow Correlates with Clinical Condition Late After the Fontan Procedure.

In the Fontan circulation, there is a substantial degree of systemic-to-pulmonary collateral flow (SPCF), which can be measured by cardiac magnetic resonance (CMR). However, the correlation between the degree of SPCF and long-term outcomes is not fully understood. We retrospectively studied 321 patients who underwent the Fontan procedure and CMR at a single center. Using CMR, we calculated SPCF as pulmonary blood flow - systemic blood flow. %SPCF was defined as SPCF ÷ pulmonary blood flow. The mean age of patients at CMR was 14.3 ± 7.5years. The average %SPCF was 13.0% ± 11.0%. With a multivariate analysis, %SPCF was significantly correlated with time (i.e., the longer the time period since the Fontan procedure, the lower the %SPCF) (p = 0.006), previous total anomalous pulmonary vein drainage (p = 0.007), a low pulmonary artery index (Nakata index) before the Fontan procedure (p = 0.04), and older age at the time of the Fontan procedure (p = 0.002). Regarding the findings after the Fontan procedure, %SPCF was significantly correlated with ventricular end-diastolic volume (p < 0.001), ventricular end-systolic volume (p < 0.001), central venous pressure (p < 0.001), plasma brain natriuretic peptide concentration (p < 0.001), hemoptysis (p = 0.009), and poor New York Heart Association functional class (p = 0.007). SPCF was correlated with clinical condition after the Fontan procedure. The importance of sufficient growth of the pulmonary vascular bed should be emphasized because the development of SPCF is believed to result from the poor condition of the pulmonary circulation.

Acute and short-term efficacy of sauna treatment on cardiovascular function: A meta-analysis.

The role of sauna bathing in cardiovascular function treatment has been increasingly explored, but insufficient attention has been paid to its efficacy. We performed a meta-analysis to provide more evidence for the efficacy of sauna treatment in cardiovascular nursing. Sixteen peer-reviewed journal articles were screened to summarize the efficacy of the sauna on cardiovascular function. Both acute (0-30 min after the sauna) and short-term (2-4 weeks following the sauna treatment) efficacies were investigated. For pooled acute efficacy, body temperature and heart rate significantly (p<0.001) grew by 0.94℃ and 17.86 beats/min, respectively; reductions of 5.55 mmHg (p<0.001) and 6.50 mmHg (p<0.001) were also observed in systolic blood pressure and diastole blood pressure, respectively. For combined short-term efficacy, left ventricular ejection fraction (LVEF), 6-min walk distance, and flow-mediated dilation (p<0.001) increased by 3.27%, 48.11 m, and 1.71%, respectively; greater amelioration in LVEF was observed in participants with lower LVEF. The proportion of patients with New York Heart Association class III and IV decreased by 10.9% and 12.2%, respectively. Systolic blood pressure, diastolic blood pressure, brain natriuretic peptide concentration, left ventricular end-diastolic dimension, cardiothoracic ratio, and left atrial dimension reduced by 5.26 mmHg (p<0.001), 4.14 mmHg (p<0.001), 116.66 pg/mL (p<0.001), 2.79 mm (p<0.001), 2.628% (p<0.05), and 1.88 mm (p<0.05), respectively, while the concentration of norepinephrine in the plasma remained unchanged. Sauna treatment was found to play a positive role in improving cardiovascular function and physical activity levels, especially in patients with low cardiovascular function. These findings reveal that thermal intervention may be a promising means for cardiovascular nursing.

The evaluation of the serum brain natriuretic peptide concentrations in preeclamptic and healthy pregnant women and its potential relationship with mean arterial blood pressure

Objective In this study, we aimed to investigate the correlation between serum brain natriuretic peptide (BNP) concentrations and blood pressure levels by comparing serum brain natriuretic peptide (BNP) concentrations in preeclamptic and normotensive pregnant women and to assess its potential role in the preeclampsia pathogenesis. Methods A total of 48 preeclamptic and 39 normotensive patients were included in the study prospectively. Systolic diastolic and mean arterial blood pressure of the pregnant women were measured. Serum BNP concentrations were measured by enzyme immunoassay method. The variable differences between the groups were analyzed by independent samples t-test. Potential correlations between the variables were assessed by Pearson’s correlation analysis. Results There was no difference between the groups in terms of age (26.18±11.49 years vs. 26.04±14.06 years), gestational age (31.59± 6.94 weeks vs. 30.17±5.72 weeks), parity (2.62±1.4 vs. 2.53±1.82) and body mass index (30.71±16.33 kg/m2 vs. 30.09±13.82 kg/m2) (p&gt;0.05). Systolic (148.66± 61.82 mmHg vs. 126.44±97.47 mmHg; p=0.015), diastolic (81.19±52.25 mmHg vs. 97.29±14.27 mmHg; p=0.019) and mean arterial pressure (113.97±41.76 mmHg vs. 96.26±27.25 mmHg; p&lt;0.001) levels were higher in the pregnant women complicated with preeclampsia. In addition, serum BNP concentrations were also higher in the preeclamptic pregnant women than the control group (139.42±62.19 pg/mL vs. 99.28±19.32 pg/mL; p=0.028). BNP levels were significantly associated with only mean arterial pressure (b=0.241, p=0.037). Also, there was a significant positive correlation between BNP levels and mean arterial pressure (r=0.406, p=0.002). Conclusion We recommend further prospective studies with wider populations to assess whether BNP levels, which increase in preeclampsia, are associated with blood pressure levels or not.

A Randomized, Controlled Pharmacokinetic and Pharmacodynamics Trial of Ambrisentan After Fontan Surgery.

To determine the pharmacokinetics, pharmacodynamics, and safety of the hepatically metabolized endothelin receptor antagonist, ambrisentan in children after Fontan surgery. Prospective, randomized, double-blind, placebo-controlled pharmacokinetic/pharmacodynamics and safety trial. Single-center, postoperative cardiac ICU. Children undergoing elective Fontan surgery. Subjects randomized on postoperative day number 1 to short-term (3 d) treatment with oral ambrisentan (2.5 mg in suspension, daily) versus placebo (4:1 randomization). Plasma drug concentrations were measured at 0.5, 1, 2, 4, and 18-36 hours after the first dose. We developed a population pharmacokinetic model in NONMEM 7.2 (Icon Solutions, Ellicott City, MD) and applied the model to dose-exposure simulations. Pharmacodynamics endpoints were assessed at baseline and 3 hours after study drug administration, using postoperative hemodynamic monitoring lines. The analysis included 16 patients, 13 on ambrisentan (77 plasma samples); median age 36 months (range, 26-72 mo), weight 13.3 kg (11.1-17.6 kg), and nine males. There were no differences in baseline characteristics between ambrisentan and controls. A one-compartment model with first-order absorption and lag-time characterized the data well. Allometrically scaled weight was the only covariate retained in the final model. Typical values for clearance and volume of distribution were lower than previously reported in adults, 1 L/hr/70 kg and 13.7 L/70 kg, respectively. Simulated exposures with doses of 0.1-0.2 mg/kg approximated therapeutic exposures in adults with pulmonary arterial hypertension receiving 5 mg or 10 mg doses. Ambrisentan lowered plasma brain natriuretic peptide concentrations (452 ± 479 to 413 ± 462; p = 0.046), Fontan pressures (16.8 ± 2.9 to 15.6 ± 2.9; p = 0.01), and indexed pulmonary vascular resistance (2.3 ± 0.9 to 1.8 ± 0.6; p = 0.01) with no drug-related adverse events. Ambrisentan clearance is reduced following Fontan surgery, perhaps reflecting abnormal hepatic metabolism in this population. The observed safety profile appears favorable and hemodynamic effects of ambrisentan may be beneficial for Fontan patients.

The Effect of Xinmailong Infusion on Sepsis-Induced Myocardial Dysfunction: a Pragmatic Randomized Controlled Trial.

Sepsis-induced myocardial dysfunction (SIMD) contributes significantly to cardiovascular dysfunction during septic shock. We aimed to evaluate the potential role of Xinmailong injection (XMLI), a polypeptide medicine extracted from Periplaneta americana, in reversing the progression of myocardial damage to SIMD in sepsis patients. This was a multicenter, randomized, double-blind, parallel-group trial. We recruited all patients consecutively admitted to intensive care units (ICUs) who were aged 18 to 85 years old and met the sepsis 3.0 criteria. The primary outcome measure was the incidence of sepsis-induced myocardial dysfunction while in the ICU. Of the 192 patients, 96 were assigned to the treatment group, and 96 to the control group. Subsequently, 41 patients [41/96 (42.7%)] in the XMLI group and 61 patients in the placebo group [61/96 (63.5%)] were confirmed to have diastolic dysfunction on the fifth day (D5). The incidence of diastolic SIMD was significantly different between the two groups (P = 0.004). There were 36 deaths in the two groups during the 28-day follow-up, with a general mortality rate of 18.8% (36/192). The 28-day mortality rates were not significantly different between the groups (P = 0.45). However, the brain natriuretic peptide (BNP) plasma concentration trends on D0, D2, and D5 significantly differed between the two groups (P = 0.049). In septic patients, XMLI decreased the occurrence rate of diastolic SIMD more effectively than the placebo. The improvement in serum BNP concentration was also greater in the XMLI group. XMLI may, therefore, effectively and safely improve cardiac function in patients with sepsis.