Cardiac Natriuretic Peptide And Cgmp Impairment In Human Decompensated Heart Failure: Employing A Novel Ex Vivo Natriuretic Peptide/GC-A/cGMP Potency Assay To Evaluate Natriuretic Peptide Therapeutic Capacity

DOPPLER ULTRASOUND ASSESSMENT OF INTRA-RENAL VENOUS FLOW IN PATIENTS WITH ACUTE DECOMPENSATE HEART FAILURE: A POTENTIAL ACUTE CARDIORENAL SYNDROME BIOMARKER

Background: Brain natriuretic peptide (BNP) is routinely measured for evaluating the severity of acute decompensated heart failure (ADHF). However, there are no other biomarkers for stratification of ADHF patients in clinical settings. Cardiac myosin I (CM-I) is one of a superfamily of motor proteins, which is mainly distributed in myocardium. Several papers reported that serum CM-I levels increased in patients with acute coronary syndrome (ACS). However, the role of CM-I in ADHF patients is not yet elucidated. Purpose: The aim of this study was to clarify the utility of CM-I in ADHF patients. Methods: We assessed 114 ADHF patients who visited our institution between December 2017 and May 2018 in a retrospective study. All patients were diagnosed ADHF using Framingham criteria. Eight ACS patients and 22 patients lacking in data of serum CM-I levels were excluded. Finally, we analyzed 84 patients. We calculated the difference in serum BNP levels between on admission and at discharge (delta BNP) as a prognostic surrogate marker. Results: Average age was 77.5 years old and 44 patients were male. Numbers of patients with NYHA III and IV were 30 and 36, respectively. Mean serum levels of BNP and Troponin T (TrT) on admission were 934.0 pg/ml and 0.092 ng/ml, respectively. Average left ventricular ejection fraction (LVEF) by echocardiography was 46.1%. Serum CM-I levels on admission and at discharge were 12.8 mg/ml and 7.30 mg/ml, respectively. Serum CM-I levels had a significant correlation with TrT levels (R=0.46, p<0.0001) and a weak correlation with BNP levels (R=0.33, p= 0.006). CM-I levels were not statistically correlated with LVEF. CM-I levels were well correlated with delta BNP(R=0.36, p= 0.0138), but TrT were not associated with delta BNP(R=0.066, p= 0.658). Conclusion: We found CM-I was associated with the difference in BNP between on admission and at discharge in ADHF patients. CM-I may be a new potential prognostic biomarker in ADHF patients.

Aim. To assess the risk factors and diagnostic significance of the N-terminal probrain natriuretic peptide (NT-proBNP) in patients with acute decompensated heart failure (ADHF) and diabetic kidney disease (DKD).Material and methods. A total of 125 patients with ADHF and type 2 diabetes (T2D) were examined. They were divided into 2 groups depending on the presence/ absence of chronic kidney disease (CKD). The first group consisted of 43 (34,4%) patients with DKD, the second — 82 (65,6%) without CKD. The inclusion criterion was the presence of ADHF and T2D. There were following exclusion criteria: cardiogenic shock, pulmonary edema, acute thromboembolic events, type 1 diabetes, prediabetes, acute coronary syndrome, stroke, prior transient ischemic attack (<1 month old), dissecting aneurysm or aortic dissection, acute valvular disorders, major surgery (<1 month old), cardiac trauma, infective endocarditis, acute hepatitis and cirrhosis, terminal CKD, alcohol abuse, non-cardiac edema, cancer, dementia and mental disorders.Results. With the development of a hypertensive crisis and an increase in diastolic blood pressure >100 mm Hg, the odds ratio (OR) and the relative risk (RR) of ADHF in patients with DKD increases by 5,1 and 4,5 times, 2,5 and 1,8 times, respectively. In the presence of grade III-V premature ventricular contractions, OR and RR of ADHF in patients with DKD were 2,6 and 1,9, respectively. OR and RR of ADHD in patients with DKD and prior stroke or transient ischemic attack were 3,8 and 3,2, respectively. Verification of anemia at a hemoglobin level of 5 mmol/l, the OR of ADHF in patients with DKD increases by 3,7 times, the OR — by 2,3 times. The NT-proBNP >1289 pg/ml is diagnostic for verifying ADHF in DKD patients with the sensitivity of 64,3% and specificity of 93,3%.Conclusion. Every third patient with ADHF and T2D is diagnosed with DKD. A certain range of risk factors for the development of ADHF in patients with DKD has been identified. As the glomerular filtration rate (GFR) decreases, the NT-proBNP level increases. With a decrease in GFR of 60 ml/min/1,73 m2 in patients with T2D, the diagnostic value of NT-proBNP >1289 pg/ml should be considered to verify ADF.

It is reported that adiponectin has a cardioprotective effect and is decreased in type 2 diabetes mellitus (DM). The effect of carperitide (atrial natriuretic peptide: ANP) on plasma adiponectin levels was evaluated in acute decompensated heart failure (ADHF) patients with and without DM. In 47 patients (DM: n=11) who were admitted with ADHF, blood samples were collected before and 7 days after administration of carperitide. The plasma levels of ANP, brain natriuretic peptide (BNP), aldosterone and adiponectin were measured. Plasma adiponectin levels were significantly increased (17.6 +/-1.5 to 19.6 +/-1.8 microg/ml, P=0.0003) concomitant with the increase in ANP and decrease in BNP 7 days after carperitide infusion. Although adiponectin levels before treatment were slightly lower in ADHF patients with DM, the % increase in adiponectin levels was significantly greater in ADHF patients with DM than in those without DM (26.7 vs 6.6%, P=0.007). In the stepwise multivariate analyses, a higher plasma aldosterone levels before treatment (P=0.04) and DM (P=0.01) were significant independent predictors of a greater % increase in adiponectin levels after treatment with carperitide. Carperitide infusion increases the plasma adiponectin level, especially in ADHF patients with DM.

Background: The blood glucose (BG) concentration (BG≧140 mg/dL) at hospitalization is reported to be the short-term prognostic predictor in patients with acute myocardial infarction. However, it’s significance in patients with acute decompensated heart failure (ADHF) has not been elucidated. Purpose: To evaluate the prognostic power of BG levels at hospitalization in the patients with ADHF. Methods: We analyzed consecutive 517 ADHF patients admitted from January 2007 to December 2013. They were divided into the high BG group (H-BG: BG≧140 mg/dL, n=215) and the low BG group (L-BG: BG<140 mg/dL, n=302) by BG levels in an emergency room. Echocardiographic findings, laboratory data and in-hospital mortality were analyzed. Results: In 517 ADHF patients, the mean age, BG levels at hospitalization, left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) were 79.7±11.8 years, 153.0±75.2 mg/dL, 52.2±15.8% and 831.5±787.9 pg/mL, respectively. There were no significant differences in age, LVEF and BNP level between H-BG and L-BG groups. The mortality rate in H-BG group was significantly higher than that in L-BG group (17.0% vs 8.1%, p=0.0081). In diabetic ADHF patients (n=138), there was no significant difference in the in-hospital mortality rate between H-BG (n=100) and L-BG (n=38) groups (13.2% vs 24.4%, p=0.1116). However, in non-diabetic ADHF patients (n=379), the in-hospital mortality rate was significantly higher in H-BG (n=115) group compared to L-BG (n=264) group (21.2% vs 5.6%, p<0.0001), and the logistic regression analysis revealed that the BG level at hospitalization could predict the in-hospital death (p=0.0381). The Kaplan-Meier survival curve demonstrated poorer prognosis in H-BG group compared to L-BG group in non-diabetic ADHF patients (Figure, p<0.0001). Conclusion: The BG concentration at hospitalization is a significant predictor of in-hospital death in ADHF patients without diabetes, but not with diabetes.

Introduction: B-type natriuretic peptide (BNP) has been widely used for the diagnosis of heart failure. Previous data suggest a lower diagnostic accuracy of BNP in HF patients with atrial fibrillation (AF). However, little is known about disproportionately low BNP levels in AF patients even during acute heart failure conditions. Hypothesis: The factors related to disproportionately low BNP might be different between AF and sinus rhythm (SR) in patients with acute decompensated heart failure (ADHF). Methods: Among 424 patients hospitalized for ADHF between January 2015 and December 2017, we divided into two groups based on the rhythm at hospital admission (AF group, n=201 and SR group, n=223) and subdivided them into four groups (Q1-Q4) according to each quartile of BNP levels at hospital admission (BNP lowest quartile (Q1) group (LB): < 320 pg/mL in SR; Q1 < 240 pg/mL in AF). Results: The proportion of patients with unexpectedly low BNP (BNP < 200 pg/mL) was higher in AF group (19.9%) than in SR group (12.1%, p=0.03). BNP was correlated with left ventricular end-diastolic volume index (LVEDVi), left ventricular ejection fraction (LVEF) in both groups (AF: r=0.28, p<0.01; r=-0.43, p<0.01, SR: r=0.41, p<0.01; r=-0.39, p<0.01, respectively) . On the other hand, BNP was positively correlated with left atrial diameter in SR group but negatively correlated in AF group (r=0.14, p=0.039 vs. r=-0.21, p<0.01, respectively, Figure). Furthermore, survival rates significantly increased along BNP tertiles in SR group. On the contrary, in AF group, Q1 (LB) did not show the highest survival rates (p=0.02, Figure). Conclusions: A higher proportion of ADHF with disproportionately low BNP was seen in AF than in SR group. In ADHF patients with AF, LB may be reflected by LA structural remodeling. Furthermore, LB was related to good prognosis in SR group, but not in AF group.

Although counter-regulation between B-type natriuretic peptide (BNP) levels and renin-angiotensin-aldosterone system (RAAS) activation in heart failure (HF) has been suggested, whether the regulation is preserved in acute decompensated heart failure (ADHF) patients remains unclear. This study aimed to determine: (1) the relationship between RAAS activation and clinical outcomes in ADHF patients, and (2) the relationships between plasma BNP levels and degrees of activation in RAAS factors. This study included ADHF patients (n=103, NYHA3-4, plasma BNP>200pg/ml). We studied the predictability of RAAS factors for cardiovascular events and the relationships between plasma BNP levels and the degrees of activation in RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events over 1year, even after accounting for plasma BNP levels (hazard ratio (HR): 1.04, CI [1.02-1.06], p<0.01) and medication such as RAAS blockers (HR: 1.03, CI [1.01-1.05], p<0.01), whereas PAC was borderline-significant (univariate analysis, p=0.06). Cut-off value of PRA (5.3ng/ml/h) was determined by AUC curve. Of the enrolled patients, higher PRA was found in 40% of them. Although no correlation between the plasma BNP levels and PRA was found (p=0.36), after adjusting for hemodynamic parameters, eGFR and medication, a correlation was found between them (p=0.01). Elevated RAAS factors were found in a substantial number of ADHF patients with high plasma BNP levels in the association with hemodynamic state, which predicts poor clinical outcomes. The measurements of RAAS factors help to stratify ADHF patients at risk for further CV events.

Background Immediate diagnosis of acute decompensated heart failure (ADHF) is essential in patients with dyspnoea. Remote Dielectric Sensing (ReDS), an electromagnetic non-invasive technology, estimates lung fluid content fast and observer-independently. In previous studies, ReDS discriminated congested heart failure patients from normal subjects with high accuracy. But not all ADHF patients have pulmonary interstitial congestion in the real world, and it is unknown if ReDS detects ADHF in consecutive patients with acute dyspnoea. Purpose To examine if ReDS can detect ADHF in consecutive dyspnoeic emergency patients and to compare ReDS with other diagnostic methods. Method This prospective observational study included consecutive patients with dyspnoea from the emergency departments. The exclusion criteria were age below 50 years, acute coronary syndrome, conditions prohibiting a supine CT scan, and no informed consent. We examined all patients immediately with ReDS, low-dose chest CT, echocardiogram, lung ultrasound (LUS), NT-proBNP, and Boston score. The Boston score used chest X-ray and clinical signs such as orthopnoea, jugular venous elevation, lung crackles and pedal oedema, and a score ≥8 equalled definite ADHF. A “LUS-score” ≥3 with at least 3 B-lines in one zone bilaterally equalled ADHF. ReDS values &amp;gt;35% lung fluid content were positive for pulmonary congestion, according to previous studies. According to ESC guidelines, an expert panel adjudicated the ADHF diagnosis based on clinical signs, chest X-ray image, NT-proBNP, echocardiographic cardiac dysfunction (HFvhd, HFrEF, HFmrEF, HFpEF), and elevated LV filling pressure. Importantly, the panel was blinded to the ReDS values. For sub-analyses, we divided ADHF patients into a “CT-congested” ADHF subgroup if an independent chest CT showed interstitial congestion. We classified ADHF patients without congestion on CT, as the “mildly-congested” subgroup. Results 97 included patients were examined within a median of 4.8 hours from admittance: 39 (40%) had ADHF, and 25 (26%) were ReDS-positive. ADHF patients had median LVEF 48%, NT-proBNP 347 pmol/l, and 85% had echocardiographic elevated LV filling pressure. ReDS detected ADHF with 46% sensitivity, 88% specificity, and 71% accuracy. The AUC for ReDS to detect ADHF (Figure 1), on a continuous scale, was similar to the Boston score (p=0.88) and the LUS score (p=0.74), but lower than NT-proBNP (p=0.02). The 21 (22%) CT-congested ADHF patients had higher ReDS values than the 18 (19%) mildly-congested ADHF patients (Figure 2, median 38% vs 30%, p&amp;lt;0.001). Furthermore, the mildly-congested ADHF patients had ReDS values similar to non-ADHF patients (median 30% vs 28%, p=0.36). Conclusion ReDS detects ADHF similarly to the Boston score and lung ultrasound but is inferior to NT-proBNP. This study suggests that ReDS primarily identifies CT-congested ADHF patients, but not the ADHF patients without interstitial congestion. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by the research fund of Bispebjerg University Hospital and Holger &amp; Ruth Hesse's Mindefond. Sensible Medical Ltd made the ReDS device available for free and provided an unrestricted grant to specifically collect the ReDS measurements. The sponsors did not affect the statistical analyses, study design, data collection, or writing of the paper.

Anp Production Is Impaired in Acute Decompensated Heart Failure

Backgrounds: Previous studies showed that worsening renal function (WRF) was associated with poor clinical outcome in acute decompensated heart failure (ADHF) patients. Hyperosmolarity is known to cause direct renal cell injury and decreases in renal blood flow and glomerular filtration rate. In ADHF setting, the plasma osmolality can be changed dramatically. However, the prognostic significance of plasma osmolality for the development of WRF in ADHF patients is unclear. Methods: We examined 320 consecutive ADHF patients who admitted to our institution between January 2013 and January 2014 from prospective registry. Patients who had acute coronary syndrome and without complete data-set at admission were excluded. Finally, 303 patients were divided into two groups according to lower plasma osmolality (below 297 mOsm/kg H2O, the cut-off value based on ROC analysis) or higher plasma osmolality (above 297 mOsm/kg H2O) at admission. WRF was defined as ≥ 0.3 mg/dl increase in serum creatinine from baseline to discharge. Results: During follow-up period (median 21 days, interquartile range 14-29), WRF was occurred in 58 patients (19.6 %). Patients with higher plasma osmolality had significantly higher incidence of WRF compared with those without (32.3% vs 13.6%, P&lt;0.01). Higher plasma osmolality was associated with more use of diuretics, higher serum creatinine level and lower hemoglobin level. There were no significant differences between the two groups in terms of age, sex, body mass index, NYHA functional class, left ventricular ejection fraction (LVEF), blood pressure, etiology of HF, cardiovascular medications other than diuretics, plasma brain natriuretic peptide (BNP) level on admission. Multivariate logistic regression analyses showed that higher plasma osmolality (OR 2.00, 95% CI 1.00-3.98, P=0.049), as well as lower hemoglobin (OR 1.22, 95% CI 1.04-1.42, P=0.012), was an independent determinant of WRF, although other variables including age, sex, serum creatinine level and use of diuretics on admission were not. Conclusions: In patients with ADHF, higher plasma osmolality on admission was an independent predictor of in-hospital WRF, suggesting the measurement of plasma osmolality might be useful for identifying patients at risk for WRF.

Introduction: Heart failure (HF) is a clinical syndrome associated with diverse metabolic disturbances. Recent studies suggest that failing heart through secretion of soluble myostatin may induce skeletal muscle wasting in HF patients and skeletal muscle plays an important role in pathogenesis of exercise intolerance in patients with chronic HF. However, the clinical significance of skeletal muscle mass in patients with acute decompensated HF (ADHF) remains unclear. Hypothesis: We hypothesized that low appendicular skeletal muscle mass could predict the occurrence of future cardiovascular (CV) events in patients with ADHF. Methods: We assessed lean body mass by dual energy X-ray absorptiometry in 96 patients with ADHF (age 72±11, left ventricular ejection fraction (LVEF) 38±15%, B-type natriuretic peptide (BNP) levels on admission 752 [377-1398] pg/ml). Low appendicular skeletal muscle mass index (ASMI, appendicular skeletal muscle mass/height 2 ) was defined according to the Asia Working Group for Sarcopenia criteria (&lt;7.0kg/m 2 in male, &lt;5.4kg/m 2 in female). ADHF patients were followed until occurring CV events (CV death, nonfatal myocardial infarction, ischemic stroke, or HF re-hospitalization). Results: ASMI significantly correlated with age (r=-0.51, P&lt;0.001), male sex (r=0.53, P&lt;0.001), body mass index (r=0.63, P&lt;0.001), systolic blood pressure on admission (r=0.21, P=0.04), and BNP levels on admission (r=-0.39, P=0.04). ADHF patients with low ASMI (n=54, 56%) had higher BNP levels (968 [552-1773] versus 498 [273-943], p=0.001) and higher rate of clinical scenario 2-3 (48% versus 12%, p=0.001) than those with normal ASMI. 42 patients developed CV events (median follow-up, 16months). Kaplan-Meier analysis demonstrated a significantly higher probability of CV events in the low ASMI group than those in the normal ASMI group (54% vs. 29%, log-rank test, P=0.02). Multivariate Cox hazard analysis identified low ASMI as an independent predictor of the CV events in patients with ADHF (hazard ratio 2.1, 95%-confidence interval 1.1-4.2, P=0.03). Conclusions: Low ASMI could predict the future CV events in patients with ADHF, irrespective of LV systolic function and other clinical profile.

Prognostic utility of B-type natriuretic peptide and 6-min walk test in patients with acute decompensated heart failure

Worsening renal function is not associated with response to treatment in acute heart failure

Background Stroke volume (SV) is the net result of cardiac dynamics and functional capacity. Notably, acute decompensated heart failure (ADHF) patients admitted highly congested and with a reduced SV (primarily wet and cold phenotype) exhibit a poorer prognosis. However, how SV may change in wet and warm phenotype during acute hospital setting remains undefined. Purpose To evaluate, in a cohort of ADHF patients, the pattern of SV changes during hospitalization. Methods Eighty-one ADHF patients (mean age 75.75±10.6 years, 59% males) warm and wet phenotype were prospectively enrolled within 24–48 hours from admission to the emergency department. In either the acute phase and at pre-discharge all patients underwent M-Mode, 2-Dimensions, Doppler and Speckle Tracking echocardiography (STE). SV and SV indexed (SVi) were estimated using the non-invasive doppler method multiplying the left ventricular outflow tract (LVOT) cross-sectional area (CSA) and the velocity time-integral (VTI) of the LVOT. Results From admission to discharge, despite a targeted decongestion we observed only minimal and non-significant changes in the average SV and SVi (SV: from 46.9±14.7 ml at admission to 47.2±15.12 at discharge, p=0.9; SVi: from 26.6±8.5 ml/m2 at admission to 27.1±8.4 ml/m2 at discharge, p=0.73). When we looked at those patients improving (Group I) vs non improving SV (Group II) we observed that subjects in Group I exhibited a significantly lower prevalence of mitral regurgitation (MR) both at admission (Group I: MR adm. 23% vs Group II: MR adm: 53% p&amp;lt;0.05) and at the pre-discharge (Group I: MR disch. 13.4% vs Group II: MR disch. 45% p&amp;lt;0.05), a significantly higher global peak atrial longitudinal strain (GPALS) at pre-discharge (Group I: GPALS disch. 17.25±6.5% vs Group II disch. 11±7.1%; p=0.04), along with a significantly greater improvement in terms of GPALS (ΔGPLAS) during hospitalization (Group I: from 13±6.9% to 17.25±6.5%, p=0.04; Group II: from 13.85±8.4% to 11±7.1%, p=0.6) (Figure 1). Interestingly, when evaluated with Pearson's coefficient, in the whole population a significant direct correlation was observed between ΔSV and ΔGPALS (r=0.67 95% CI 0.4–0.7, p&amp;lt;0.001) (Figure 2). Conclusions In ADHF patients, the wet and warm phenotype displays a decreased forward SV which does not improve after decongestion therapy on average variations. In this context, the coexistence of LA impairment and hemodynamically significant MR seems to play a key role whereas, LA functional properties recover at least in part in patients who are able to show a SV improvement. Further analysis are necessary to test whether a lack of SV improvement in the short term may impact the long-term outcome. Funding Acknowledgement Type of funding source: None

The aim of this study was to assess the prevalence of abnormal liver function tests (LFTs) and the associated clinical profile and outcome(s) in acute decompensated heart failure (ADHF) patients. Alteration in LFTs is a recognized feature of ADHF, but prevalence and outcomes data from a broad contemporary cohort of ADHF are scarce and the mechanism(s) of ADHF-induced cholestasis is unknown. We conducted a post hoc analysis of SURVIVE, a large clinical trial including ADHF patients treated with levosimendan or dobutamine. All LFTs were available in 1134 patients at baseline. Abnormal LFTs were seen in 46% of ADHF patients: isolated abnormal alkaline phosphatase (AP) was noted in 11%, isolated abnormal transaminases in 26%, and a combination of abnormal AP and transaminases in 9%. Abnormal AP was associated with marked signs of systemic congestion and elevated right-sided filling pressure. Abnormal AP had no relationship with 31-day mortality but was associated with worse 180-day mortality (23.5 vs. 34.9%, P = 0.001 vs. patients with normal AP). Abnormal transaminases were associated with clinical signs of hypoperfusion and with greater 31-day and 180-day mortality compared with normal transaminase profiles (17.6 vs. 8.4% and 31.6 vs. 22.4%, respectively; both P < 0.001). There was no additive value of abnormal AP plus abnormal transaminase on a long-term outcome. Abnormal LFTs were present in about a half of patients presenting with ADHF treated with inotropes. Abnormal AP and abnormal transaminases were associated with specific clinical, biological, and prognostic features, including a short-term overmortality with increased transaminases but not with biological signs of cholestasis, in ADHF patients.