Mid-regional Pro-atrial Natriuretic Peptide Research Articles

Predictive Value of Midregional Pro-Atrial Natriuretic Peptide for Cardioembolic Stroke in Hyperacute Ischemic Stroke.

Predictive Value of Midregional Pro-Atrial Natriuretic Peptide for Cardioembolic Stroke in Hyperacute Ischemic Stroke.

Biomarkers to improve functional outcome prediction after ischemic stroke: Results from the SICFAIL, STRAWINSKI, and PREDICT studies.

Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores. We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset). Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance. Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious.

Biomarkers for predicting atrial fibrillation: An explorative sub-analysis of the randomised SCREEN-AF trial

Background Atrial fibrillation (AF) is a common treatable risk factor for stroke. Screening for paroxysmal AF in general practice is difficult, but biomarkers might help improve screening strategies. Objectives We investigated six blood biomarkers for predicting paroxysmal AF in general practice. Methods This was a pre-specified sub-study of the SCREEN-AF RCT done in Germany. Between 12/2017-03/2019, we enrolled ambulatory individuals aged 75 years or older with a history of hypertension but without known AF. Participants in the intervention group received active AF screening with a wearable patch, continuous ECG monitoring for 2x2 weeks and usual care in the control group. The primary endpoint was ECG-confirmed AF within six months after randomisation. High-sensitive Troponin I (hsTnI), brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), N-terminal pro atrial natriuretic peptide (NT-ANP), mid-regional pro atrial natriuretic peptide (MR-pro ANP) and C-reactive protein (CRP) plasma levels were investigated at randomisation for predicting AF within six months after randomisation. Results Blood samples were available for 291 of 301 (96.7%) participants, including 8 with AF (3%). Five biomarkers showed higher median results in AF-patients: BNP 78 vs. 41 ng/L (p = 0.012), NT-pro BNP 273 vs. 186 ng/L (p = 0.029), NT-proANP 4.4 vs. 3.5 nmol/L (p = 0.027), MR-pro ANP 164 vs. 125 pmol/L (p = 0.016) and hsTnI 7.4 vs. 3.9 ng/L (p = 0.012). CRP levels were not different between groups (2.8 vs 1.9 mg/L, p = 0.1706). Conclusion Natriuretic peptide levels and hsTnI are higher in patients with AF than without and may help select patients for AF screening, but larger trials are needed.

Vasoactive peptides as biomarkers for the prediction of retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a major complication in preterm infants. We assessed if plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) serve as early markers for subsequent ROP development in preterm infants <32 weeks gestation. Prospective, two-centre, observational cohort study. MR-proANP and CT-proET1 were measured on day seven of life. Associations with ROP ≥ stage II were investigated by univariable and multivariable logistic regression models. We included 224 infants born at median (IQR) 29.6 (27.1-30.8) weeks gestation and birth weight of 1160 (860-1435) g. Nineteen patients developed ROP ≥ stage II. MR-proANP and CT-proET1 levels were higher in these infants (median (IQR) 864 (659-1564) pmol/L and 348 (300-382) pmol/L, respectively) compared to infants without ROP (median (IQR) 299 (210-502) pmol/L and 196 (156-268) pmol/L, respectively; both P < 0.001). MR-proANP and CT-proET1 levels were significantly associated with ROP ≥ stage II in univariable logistic regression models and after adjusting for co-factors, including gestational age and birth weight z-score. MR-proANP and CT-proET1 measured on day seven of life are strongly associated with ROP ≥ stage II in very preterm infants and might improve early prediction of ROP in the future. Plasma levels of midregional pro-atrial natriuretic peptide and C-terminal pro-endothelin-1 measured on day seven of life in very preterm infants show a strong association with development of retinopathy of prematurity ≥ stage II. Both biomarkers have the potential to improve early prediction of retinopathy of prematurity. Vasoactive peptides might allow to reduce the proportion of screened infants substantially.

Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Literature Review.

Hospital-acquired pneumonia (HAP) and its subtype, ventilator-associated pneumonia (VAP), remain two significant causes of morbidity and mortality worldwide, despite the better understanding of pathophysiological mechanisms, etiology, risk factors, preventive methods (bundle of care principles) and supportive care. Prior detection of the risk factors combined with a clear clinical judgement based on clinical scores and dosage of different inflammatory biomarkers (procalcitonin, soluble triggering receptor expressed on myelloid cells type 1, C-reactive protein, mid-regional pro-adrenomedullin, mid-regional pro-atrial natriuretic peptide) represent the cornerstones of a well-established management plan by improving patient's outcome. This review article provides an overview of the newly approved terminology considering nosocomial pneumonia, as well as the risk factors, biomarkers, diagnostic methods and new treatment options that can guide the management of this spectrum of infections.

Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure

BackgroundNatriuretic peptide (NP) elevations are prognostic in heart failure (HF), but relative atrial NP deficiency in acute HF has been suggested. ObjectivesThe authors compared plasma concentrations and relative strength of associations of A- and B-type NPs with cardiac structure/function and clinical outcomes in HF. MethodsMidregional pro–atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and N-terminal pro–B-type natriuretic peptide (NT-proBNP) were measured in patients with compensated HF in a prospective, multicenter study. The primary outcome was a composite of HF-hospitalization or all-cause mortality. Secondary outcomes included individual primary outcome components and cardiovascular admission. ResultsAmong 1,278 patients (age 60.1 ± 12.1 years, 82% men, left ventricular ejection fraction [LVEF] 34% ± 14%), median concentrations of MR-proANP were 990 pg/mL (Q1-Q3: 557-1,563 pg/mL), NT-proBNP 1,648 pg/mL (Q1-Q3: 652-3,960 pg/mL), and BNP 291 pg/mL (Q1-Q3: 103-777 pg/mL). No subpopulation with inappropriately low MR-proANP (relative to BNP/NT-proBNP) was observed. Clinical event rates were similar for biomarker tertiles. Increments in MR-proANP exhibited steeper associations with concurrent shifts in left ventricular size, diastolic indexes and LVEF than BNP/NT-proBNP at baseline and serially (P < 0.05), and lower odds of beneficial left ventricular reverse remodeling: OR: 0.35 (95% CI: 0.18-0.70). In single-biomarker models, MR-proANP(log10) was associated with the highest hazard (4 to 6 times) for each outcome. In multimarker models, independent associations were observed for the primary outcome (MR-proANP and NT-proBNP), HF-hospitalization and cardiovascular admission (MR-proANP only), and all-cause mortality (NT-proBNP only) (P < 0.05). The discriminative value of MR-proANP was superior to BNP/NT-proBNP (HF-hospitalization) and BNP (primary outcome) (P < 0.05). ConclusionsMR-proANP was not inappropriately low relative to concurrent BNP/NT-proBNP values. Proportional increments in MR-proANP were more pronounced than for B-peptides for given decrements in cardiac structure/function. MR-proANP offered greater independent predictive power overall.

Admission of patients with chest pain and/or breathlessness from the emergency department in relation to risk assessment and copeptin levels – an observational study

Background: One of the most critical decisions that emergency department (ED) physicians make is the discharge versus admission of patients. We aimed to study the association of the decision in the ED to admit patients with chest pain and/or breathlessness to a ward with risk assessment using the Rapid Emergency Triage and Treatment System (RETTS), the National Early Warning Score (NEWS), and plasma levels of the biomarkers copeptin, midregional proadrenomedulin (MR-proADM), and midregional proatrial natriuretic peptide (MR-proANP).&#x0D; Methods: Patients presenting at the ED with chest pain and/or breathlessness with less than one week onset were enrolled. Patients were triaged according to RETTS. NEWS was calculated from the vital signs retrospectively.&#x0D; Results: Three hundred and thirty-four patients (167 males), mean age 63.8 ± 16.8 years, were included. Of which, 210 (62.8%) patients complained of chest pain, 65 (19.5%) of breathlessness, and 59 (17.7%) of both. Of these, 176 (52.7%) patients were admitted to a ward, and 158 (47.3%) patients were discharged from the ED. In binary logistic models, age, gender, vital signs (O2 saturation and heart rate), NEWS class, and copeptin were associated with admission to a ward from the ED. In receiver-operating-characteristics (ROC) analysis, copeptin had an incremental predictive value compared to NEWS alone (P = 0.002).&#x0D; Conclusions: Emergency physicians’ decisions to admit patients with chest pain and/or breathlessness from the ED to a ward are related to age, O2 saturation, heart rate, NEWS category, and copeptin. As an independent predictive marker for admission, early analysis of copeptin might be beneficial when improving patient pathways at the ED.

Exercise MR-proANP unmasks latent right heart failure in CTEPH

Abstract Background Chronic right heart failure is the major determinant of outcome in chronic thromboembolic pulmonary hypertension (CTEPH). Thus, its early detection is crucial for optimal patient management. Hemodynamic assessment with invasive right heart catheterization and the measurement of natriuretic peptides at rest are established diagnostic tools in this context. An elevated right atrial pressure (RAP) is a sensitive parameter of right right heart failure. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a natriuretic peptide that reflects right atrial stress levels. There is a growing recognition of exercise diagnostics in the assessment of right heart failure, particularly in patients with normal or borderline findings at rest. There are no data on the dynamics of MR-proANP in correlation to RAP during physical exercise. Purpose The present study was designed to investigate the dynamics of RAP and MR-proANP during physical exercise in patients with CTEPH and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure. Methods This observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP &amp;gt;15 mmHg as suggestive of right heart failure. Results During eRHC mean RAP increased from 6±4 mmHg to 16±7 mmHg (p&amp;lt;0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs=0.61; p&amp;lt;0.001; figure 1a) and at peak exercise (rs=0.66; p&amp;lt;0.001; Figure 1b). Furthermore, the relative percent increase in MR-proANP correlated with the relative percent increase in eRAP (rs=0.52; p&amp;lt;0.001; Figure 1c) Logistic regression analysis revealed the peak MR-proANP level (B=0.058; p=0.004) and the right atrial area (B=0.389; p&amp;lt;0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC=0.81) and recovery level ≥159 pmol/L (AUC=0.82) predicted an eRAP &amp;gt;15 mmHg. Physical exercise unmasked RH failure in 39% of patients with normal RAP at rest; they were also characterized by a more distinct increase in MR-proANP levels (p=0.005) and higher peak (p&amp;lt;0.001) and recovery levels (p&amp;lt;0.001). Conclusions RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients, which may be useful in estimating prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): SFB 1213 area CP-01 projectWilliam G. Kerckhoff-FoundationKerckhoff Heart Research Institute (KHFI)German Center for Cardiovascular Research (DZHK)

The Prognostic Value of Cardiac Biomarkers in Patients with Acute Myocardial Infarction during and after Hospitalization

Objective: Myocardial infarction (MI) carries a strong risk of death and the development of major adverse cardiovascular events (MACE). A number of biomarkers have been proposed for risk stratification among patients with MI. The aim of this study was to determine whether elevated galectin-3 and midregional-pro atrial natriuretic peptide (MR-proANP) levels can be used as predictors of MACE in patients with acute myocardial infarction (AMI). Methods: Plasma levels of galectin-3 and MR-proANP were collected from 96 patients following their first AMI hospitalised in our clinic over the course of a year. Samples were taken on admission, and on the first and fifth day of hospitalization. During hospitalization, all patients were followed up for the occurrence of early major adverse cardiac events (MACE), defined as sudden cardiac arrest, new onset atrial fibrillation and need to use pressor amines. All patients were also followed up twelve months after AMI for the occurrence of late MACE defined as cardiac death, reinfarction and need for unscheduled PCI. Results: Patients who experienced early MACE had significantly higher galectin-3 and MR-proANP levels assessed on admission (p = 0.007, p = 0.003). ROC curve analysis found also galectin-3 concentration assessed on admission to be a strong predictor of late MACE (AUC = 0.75, p = 0.0061). MRproANP does not appear to have any value in predicting late MACE. Conclusions: A high concentration of galectin-3 and MR-proANP observed on admission in patients with acute myocardial infarction has significant prognostic value: it may identify patients at high risk of early adverse cardiac events after AMI. In contrast to MR-proANP, a high concentration of galectin-3 observed on admission may also identify patients at high risk of late MACE.

Mid-regional plasma pro-atrial natriuretic peptide and stroke volume responsiveness for detecting deviations in central blood volume following major abdominal surgery.

BackgroundA reduced central blood volume is reflected by a decrease in mid‐regional plasma pro‐atrial natriuretic peptide (MR‐proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head‐down tilt (HDT). We determined plasma MR‐proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account.MethodsPatients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR‐proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered.ResultsPlasma MR‐proANP decreased for patients undergoing gastroesophageal surgery (−9% [95% CI −3.2 to −15.3], p = .004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR‐proANP and fluid balance were correlated (r = .352 [95% CI 0.031–0.674], p < .001). In contrast, plasma MR‐proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR‐proANP and fluid balance, and no patient was fluid responsive.ConclusionPlasma MR‐proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.

Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) Study Protocol

Cardiac rhythm monitoring is performed to search for atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA). Prolonged cardiac rhythm monitoring increases AF detection but is challenging to implement in many healthcare settings and is not needed for all people after ischaemic stroke/TIA. We aimed to develop and validate a model that includes clinical, electrocardiogram (ECG), blood-based, and genetic biomarkers to identify people with a low probability of AF detection after ischaemic stroke or TIA. We will recruit 675 consenting participants who are aged over 18 years, who were admitted with ischaemic stroke or TIA in the 5 days prior, who are not known to have AF, and who would be suitable for anticoagulation if AF is found. We will collect baseline demographic and clinical data, a 12-lead ECG, and a venous blood sample for blood biomarkers (including midregional pro-atrial natriuretic peptide, MRproANP) and genetic data. We will perform up to 28 days of cardiac rhythm monitoring using an R-test or patch device to search for AF in all participants. The sample size of 675 participants is based on true sensitivity of 92.5%, null hypothesis sensitivity of 80%, 80% power, and 5% significance. The primary outcome is AF detection ≥30 s duration during 28 days of cardiac rhythm monitoring. Secondary outcomes are AF detection at 1-year, recurrent cardiovascular events, and mortality and will be identified by electronic linkage and telephone follow-up. The results will guide the development of a more personalized care pathway to search for AF after ischaemic stroke or TIA. This could help to reduce cardiac rhythm monitoring for people with a low probability of AF detection and allow more intensive cardiac monitoring to be focused on people who are more likely to have AF and benefit. Participants will be consented for their data to be used in future research studies, providing a rich resource for stroke and cardiovascular research communities.

Differential Impact of Biologic Therapy on Heart Function Biomarkers in Rheumatoid Arthritis Patients: Observational Study on Etanercept, Adalimumab, and Tocilizumab.

Rheumatoid arthritis (RA) represents the most frequent form of inflammatory arthritis, affecting approximately 1% of the population worldwide. The introduction of novel therapeutic strategies targeting proinflammatory cytokines (TNF-α and interleukin-6) revolutionized the treatment of RA. This kind of treatment, although effective in a substantial portion of patients, may potentially cause many side effects. Among them, cardiovascular safety is one of the main concerns. In the present study, we investigated the impact of treatment with anti-TNF-α and anti-IL-6 agents on heart function and levels of heart function biomarkers. To measure this, we used cardiac function biomarkers, such as NT-pro Brain Natriuretic Peptide, mid regional pro-Atrial Natriuretic Peptide, Galectin-3, and Heart-Type Fatty Acid-Binding Protein and compared them to patients treated with methotrexate as well as healthy controls. Patients treated with biologics were characterized by low disease activity or were in remission. The disease activity in these groups was significantly lower than in the methotrexate group. All patients recruited for the study were characterized by normal heart function measured using echocardiography (EF>50%). With the exception of MR-proANP between tocilizumab and adalimumab (median: 1.01 vs. 0.49 nmol/L, p<0.05), we failed to observe any significant differences in biomarkers levels between groups treated with biologics. Contrary to this, patients on MTX showed higher NT-proBNP levels compared to adalimumab and healthy controls (p<0.05 for both). Striking differences have been shown in regard to H-FABP. The levels of these biomarkers were elevated in all biologics and the methotrexate group compared to healthy controls. As this biomarker reflects potential heart injury, we suggest that heart damage proceeds in a continuous manner in RA patients despite effective treatment and attainment of remission/low disease activity. This finding, however, should be verified in a larger cohort of RA patients to ascertain if the routine assessment of H-FABP may be useful for the detection of patients with RA who are at risk of development of heart damage.

Protective effect of sacubitril/valsartan (Entresto) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy.

Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n=6). Next, four groups of pigs were followed for 15 days (n=24) after PN (one-third right kidney, 60min ischaemia) + Entresto (49/51mg/day; n=8), PN+vehicle (n=8), sham+Entresto (49/51mg/day; n=4) and sham+vehicle (n=4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25± 6mL/min, left 31± 7mL/min) accounted for the total GFR (56± 14mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23± 6mL/min, P<.05)and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.

MR-proANP measured at admission is associated with incident atrial fibrillation in STEMI patients.

Atrial fibrillation (AF) is common following ST-segment elevation myocardial infarction (STEMI). Increased blood levels of mid regional pro atrial natriuretic peptide (MR-proANP) have been associated with a greater risk of incident AF. However, knowledge of the value of MR-proANP in predicting incident AF after STEMI is sparse. To assess whether MR-proANP measured at admission is associated with development of incident AF in patients with STEMI. 673 STEMI patients with no history of AF treated with primary percutaneous coronary intervention (pPCI) were prospectively enrolled from September 2006 to December 2008. Blood samples were drawn before the procedure. MR-proANP was measured by an automated processing assay. End point was incident AF. Median follow-up time was 5.5years (interquartile-range 4.7-6.0), during which 63 patients developed AF. In a multivariable Cox regression model adjusted for relevant clinical and biochemical variables, MR-proANP was significantly associated with the development of AF (HR 1.18 per 100pmol, 95% CI 1.11-1.28, p < 0.001). In a subgroup of patients who underwent echocardiography (N = 360), MR-proANP remained significantly associated with the development of AF (HR 1.39 per 100pmol, 95% CI 1.13-1.71, p = 0.002) after adjusting for clinical and biochemical variables and left ventricular ejection fraction. When stratifying patients according to tertiles of MR-proANP, patients in the upper tertile displayed an 11 times greater risk of developing AF during follow-up as compared to patients in the lower tertile (HR 11.1, 95% CI 4.4-28.2, p < 0.001). Plasma MR-proANP measured at admission is an independent predictor of incident AF after STEMI.

Diastolic stress echocardiography and biomarkers in patients with preserved left ventricle ejection fraction and heart failure symptoms.

Diastolic dysfunction (DD) is a diagnostic challenge in clinical practice. Our study aimed to evaluate the value of diastolic stress echocardiography (DSE) and heart failure (HF) biomarkers in patients with preserved left ventricular ejection fraction (LVEF) and HF symptoms. All the consecutive patients with HF symptoms, preserved LVEF, and suspected DD were examined on transthoracic echocardiography (TTE) and DSE using the protocol according to the American Society of Echocardiography recommendations. Moreover, blood samples were taken 30 minutes before and after DSE for the following lab markers: N-terminal pro-B type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), and serum soluble ST2 receptor (ST2). The study group included 80 patients (mean [standard deviation, SD] age, 69 (8.1) years; 25% males) with dyspnea (New York Heart Association classification IIa - 53; IIb - 17; III - 10) and risk factors: hypertension (96%), diabetes (41%), obesity (56%), and known coronary artery disease (10%). The rest transthoracic echocardiography (TTE) showed preserved systolic function (mean [SD], LVEF 61.1 [10.5]%) and normal or indeterminate diastolic function. DSE revealed a positive result for diastolic dysfunction in 17 patients (21%). The receiver operating characteristic (ROC) analysis showed that age (the area under the curve [AUC], 0.725; P < 0.01), left atrial volume indexed for body surface area [LAVI] rest (AUC, 0.722; P < 0.01), E/e' rest (AUC, 0.790; P < 0.01), and baseline NT-proBNP (AUC, 0.713; P < 0.01) predicted positive DSE. Other parameters, including body mass index, baseline E/A, DT, or e' were not predictive of DSE results. DSE revealed diastolic dysfunction in 21% of study patients and improved the diagnostic value of echocardiography. Rest NT-proBNP, but not MR-proANP and ST2, provided a diagnostic value for diastolic dysfunction.

Circulating Biomarkers Predict Symptomatic but Not Asymptomatic Carotid Artery Stenosis

Background: Subjects exposed to risk factors such as age, gender, hypertension, diabetes mellitus, and smoking are prone to atherosclerotic events. Aims: The main aim of this longitudinal cohort study was to determine whether the role of novel plasma biomarkers for atherosclerotic carotid artery disease is different in subjects developing symptomatic carotid artery stenosis (CAS), as opposed to those with incident asymptomatic CAS. Methods: The following biomarkers were measured in 5,550 middle-aged subjects in a population-based cohort study: C-reactive protein (CRP), lipoprotein-associated phospholipase A2 mass and activity, proneurotensin, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT pro-BNP), copeptin, and cystatin C. After exclusion of those with prevalent CAS, subjects were thereafter followed in national patient registers for 23.4 (interquartile range 19.5–24.3) years regarding incident symptomatic and asymptomatic CAS. Results: Among 110 patients with confirmed incident CAS, 56 were symptomatic and 54 were asymptomatic. When including conventional risk markers in a Cox regression analysis, NT pro-BNP (hazard ratio [HR] 1.59; 95% confidence interval [CI]: 1.20–2.11), MR-proADM (HR 1.40; CI: 1.13–1.73), cystatin C (HR 1.21; CI: 1.02–1.43), and CRP (HR 1.53; CI: 1.13–1.73) were independently associated with incident symptomatic CAS, whereas no plasma biomarker was associated with incident asymptomatic CAS. Conclusion: Plasma biomarkers NT pro-BNP, MR-proADM, cystatin C, and CRP were independently associated with incident symptomatic CAS, whereas no such association could be demonstrated with incident asymptomatic CAS. As these biomarkers indicate future development of clinically relevant atherosclerotic CAS, their potential utility in relation to intensified preventive measures and selection of potential candidates for carotid surgery should be further evaluated.

Novel predictive role for mid-regional proadrenomedullin in moderate to severe aortic stenosis

ObjectiveWe investigated the prognostic significance of selected known and novel circulating biomarkers in aortic stenosis (AS).MethodsN-terminal pro-BNP (NT-proBNP), high-sensitivity troponin-T (hsTnT), growth differentiation factor-15 (GDF-15), suppression of tumorigenicity-2 (ST2), mid-regional...

Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN).

Simple SummaryCardiovascular disease is common in patients with small cell lung cancer, partly reflecting its high correlation with smoking. Cardiovascular comorbidities may limit patient tolerance to cytotoxic drugs, thereby influencing the choice and intensity of treatment and, ultimately, patient survival. In light of the challenges relating to assessing cardiovascular status clinically in newly diagnosed lung cancer, objective biomarkers of cardiovascular vulnerability are warranted. Here, we show that circulating levels of ST2, an established biomarker in heart failure, and adrenomedullin, a vasodilator peptide known to reflect several aspects of cardiovascular status, strongly correlate with survival in small cell lung cancer. Our data, which are based on a large, randomized trial cohort, suggest the potential use of cardiovascular biomarkers in guiding clinicians in making individualized treatment decisions.Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44–3.98; p = 0.001) and 2.18 (95% CI 1.35–3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; p < 0.001) and 3.49 (95% CI 1.84–6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.

Effect of a 3-Week Treatment with GLP-1 Receptor Agonists on Vasoactive Hormones in Euvolemic Participants

Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) exert cardiovascular benefits by reducing plasma glucose, body weight, and blood pressure. The blood pressure-lowering effect may be mediated by angiotensin II (ANG II) suppression and consecutive natriuresis. However, the role of ANG II and other vasoactive hormones on GLP-1 RA treatment has not been clearly defined. This work aimed to investigate the effect of a 3-week treatment with the GLP-1 RA dulaglutide on vasoactive hormones, that is, renin, ANG II, aldosterone, mid-regional proatrial natriuretic peptide (MP-proANP), and natriuresis in euvolemic participants. Randomized, double-blinded, placebo-controlled, crossover trials were conducted at University Hospital Basel, Switzerland. A total of 54 euvolemic participants, including 20 healthy individuals and 34 patients with primary polydipsia, received a subcutaneous injection of dulaglutide (Trulicity) 1.5 mg and placebo (0.9% sodium chloride) once weekly over a 3-week treatment phase. After a 3-week treatment phase, dulaglutide showed no effect on plasma renin, plasma ANG II, or plasma aldosterone levels in comparison to placebo. Natriuresis remained unchanged or decreased on dulaglutide depending on the measured parameter. Dulaglutide significantly decreased plasma MR-proANP levels (treatment effect: 10.60 pmol/L; 95% CI, -14.70 to -7.90; P < .001) and systolic blood pressure (median: 3 mm Hg; 95% CI, -5 to 0; P = .036), whereas heart rate increased (median: 5 bpm; 95% CI, 3-11; P < .001). In euvolemic participants, a 3-week treatment of dulaglutide reduced systolic blood pressure independently of plasma renin, ANG II, or aldosterone levels and urinary sodium excretion. The reduction in MR-proANP might be secondary to reduced arterial pulse pressure.

Uncoupling between intravascular and distending pressures leads to underestimation of circulatory congestion in obesity.

Patients with obesity frequently present with dyspnoea. Biomarkers that reflect wall stress are often used to evaluate circulatory congestion and help determine whether dyspnoea is of cardiac causes. Patients with obesity display greater external restraint on the heart, which may alter relationships between intravascular pressures and stress markers. Subjects with unexplained dyspnoea (n= 212) underwent cardiac catheterization with simultaneous echocardiography. Blood sampling was performed in a subset (n= 58). Relationships between echocardiographic and blood biomarkers of circulatory congestion and directly-measured haemodynamics were compared between participants with severe obesity [body mass index (BMI) ≥35 kg/m2 , Group B) and those without (BMI <35 kg/m2 , Group A). Circulatory congestion was assessed by pulmonary capillary wedge pressure (PCWP), and vascular distending pressure was assessed by left ventricular transmural pressure (LVTMP). As compared to Group A, participants in Group B displayed higher PCWP relative to N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide, troponin T, and growth differentiation factor-15 (all p< 0.01). In contrast, the relationships between LVTMP and the biomarkers were superimposable. Echocardiographic biomarkers revealed the same pattern: PCWP was higher for any E/e' ratio in Group B compared to Group A, but the relationship between LVTMP and E/e' was similar. In contrast, levels of C-terminal pro-endothelin-1 and mid-regional pro-adrenomedullin were more robustly correlated with PCWP (r=0.67 and r=0.62, both p< 0.0001), with no differential relationship based upon BMI. Non-invasive haemodynamic markers underestimate circulatory congestion in patients with obesity, an effect that appears related to uncoupling between cardiac wall stress and intravascular pressures. This may lead to systematic under-recognition of congestion in patients with obesity.