Reduction In NT-proBNP Levels Research Articles

Combined effects of growth hormone and testosterone replacement treatment in heart failure.

AimsAlthough preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF.Methods and resultsFive stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline‐based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months. Each patient underwent a complete M‐mode, two‐dimensional, and Doppler echocardiographic examination, and an incremental symptom‐limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2). One‐year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT‐proBNP levels (−35.1%, P < 0.01). Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01). These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow‐up period.ConclusionsOur preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.

P4160Safety and efficacy of triple combination therapy with parenteral prostanoids in patients with Eisenmenger physiology

Abstract Aim While combination therapy is currently strongly advocated for idiopathic pulmonary arterial hypertension (PAH) patients, evidence to support its use in patients with PAH related to congenital heart disease (CHD), especially patients with Eisenmenger syndrome, is lacking. We evaluated the efficacy and safety of sequential triple combination therapy with parenteral prostanoids after failure of double oral therapy in patients with PAH-CHD and Eisenmenger physiology. Methods This is an international, multicentre, retrospective cohort study conducted in adult patients with Eisenmenger physiology on double oral PAH therapy in whom intravenous or subcutaneous prostanoid treatment was added due to clinical deterioration or failure to reach the treatment goals. Clinical status, 6-minute walk test distance (6MWD), biomarkers and haemodynamics were assessed at baseline and during the follow-up. Results A total 28 patients with Eisenmenger syndrome (6 [21%] male, age 37.6±14.3 years) were included. A post-tricuspid shunt was present in 16 (57%), 86% of whom had a ventricular septal defect. The majority (89%) were treated with subcutaneous treprostinil. At 27±14 months follow-up, WHO functional class improved in 18 (64%), remained unchanged in 8 (29%), and deteriorated in 2 (7%) patients. There was also an increase in 6MWD (mean 339±145 versus 233±140m, p=0.0001, fig 1A) and a reduction in NT-proBNP levels (median 1125 [123–5882] versus 3087 [234–7428] pg/mL, p&lt;0.0001, fig 1B). On follow-up cardiac catheterization, an improvement in right atrial pressure (8±2 versus 11±5 mmHg, p=0.01), mean pulmonary artery pressure (68±12 versus 72±17 mmHg, p=0.005), cardiac index (2.3±0.3 versus 2.0±0.5 l/min/m2, p=0.005, fig 1C), and pulmonary vascular resistance (17±7 versus 21±10, p=0.008, fig 1D), was observed compared to baseline. No patients discontinued treatment. Five (18%) patients died during follow up. Figure 1 Conclusions Triple combination therapy with subcutaneous treprostinil or endovenous epoprostenol in patients with Eisenmenger syndrome is safe and well tolerated at 2 years follow-up, resulting in a significant improvement in clinical status, exercise tolerance and haemodynamics.

Hemodynamic Congestion at Hospital Discharge Predicts Rehospitalization during Short Term Follow Up in Acute Heart Failure Patients

Background: Hemodynamic congestion is an increase in left ventricular diastolic pressure (LVEDP) without clinical symptoms and signs of congestion. Current acute heart failure (AHF) treatment goals only focused on improving clinical congestion. The purpose of this study was to investigate whether hemodynamic congestion measured by NT-proBNP level and ePCWP at hospital discharge could predict short term clinical outcomes in AHF patients.&#x0D; Method: This prospective cohort study was conducted at dr. Saiful Anwar General Hospital Malang from January to July 2018. All patients got AHF treatment according to the 2016 ESC guidelines for heart failure. All patients were discharged without symptoms and signs of clinical congestion. Hemodynamic congestion at hospital discharge was defined as failure of treatment during hospitalization to achieve a reduction in NT-proBNP level &gt;30% and/or ePCWP at hospital discharge &gt;16 mmHg. NT-proBNP level and ePCWP were measured at 0-12 hours after hospital admisssion and at hospital discharge. ePCWP was measured using echocardiography. The clinical outcomes assessed were AHF rehospitalization and cardiovascular mortality within 30 days after hospitral discharge. Subgroup analysis was performed to determine therapeutic regimens that are effective in improving hemodynamic congestion.&#x0D; Result: A total of 33 AHF patients were included in this study. 48% patients were discharged with hemodynamic congestion and 52% patients discharged without hemodynamic congestion. Patients with hemodynamic congestion at hospital discharge showed a higher rehospitalization within 30 days (8 [50%] vs 1 [5.9%]; P = 0.007). Mortality within 30 days in both groups did not show a significant difference (2 [12.5%] vs 0 [0%]; P = 0.277). Treatment regiment of optimal dose of ACEi/ARB, β-blockers, and diuretics was associated with improvement of hemodynamic congestion (P = 0.026; r = 0.454), a decrease in NT-proBNP&gt; 66% (P = 0.02; r = 0,574), and achievement of ePCWP &lt;16 (P = 0,013; r = 0,493) at hospital discharge in HFrEF patients.&#x0D; Conclusion: This study showed that hemodynamic congestion assessed with NT-proBNP level and ePCWP at hospital discharge increased 30 day rehospitalization in AHF patients. In HFrEF, improvements in hemodynamic congestion can be achieved by giving the treatment regiment of optimal dose of ACEi/ARB, β-blockers, and diuretics.&#x0D; Keyword: Acute heart failure, hemodynamic congestion, NT-proBNP, ePCWP

A Pilot Study: Decreased Hospitalization in Elderly Heart Failure Patients While on Sacubitril-Valsartan Combination

Introduction Sacubitril-Valsartan combination (SVC) is new to the heart failure (HF) armamentarium. SVC, in addition to HF goal directed medical therapy (GDMT), is indicated to reduce the risk of cardiovascular (CV) death and HF hospitalizations in patients with reduced ejection fraction (HFrEF). PARADIGM-HF was stopped early due to overwhelming efficacy when compared to Enalapril. SVC dosed to the target 97/103 mg twice daily, reduced the primary composite outcomes of CV death or first HF hospitalization by 20%. HF guidelines recommend SVC as an option in patients with HFrEF. In PIONEER-HF, compared to Enalapril, SVC had a greater time-averaged reduction in NT-proBNP levels (25% vs. 47%, respectively) from baseline through weeks 4 and 8 after HF hospitalization. This combination was safe and well-tolerated in both studies. Hypothesis In PARADIGM-HF and PIONEER-HF the mean age was 62 years and the majority NYHA FC II to III. Results were difficult to extrapolate in patients &gt75 years with HFrEF. This group would be excluded from advanced therapies, i.e. cardiac transplant or durable mechanical circulatory support. HF GDMT optimization is the goal for this population. In clinical trials, SVC shows significant reduction in CV death and/or HF hospitalizations compared to Enalapril. We hypothesize that the clinical outcomes of patients &gt75 years with HFrEF receiving SVC would be favorable. Methods A retrospective chart review was conducted in a community hospital between January 2016 and December 2017. Subjects were identified via electronic health record. Inclusion criteria included age &gt 75 years, left ventricular ejection fraction &lt 40%, on maximally tolerated GDMT and SVC initiated during hospitalization. Subjects were excluded if SVC was not continued at discharge or lost to follow up. The clinical outcomes were CV death or first 30-day HF readmission, change in renal function or blood pressure. Descriptive statistics were used for data analysis. Results Inclusion criteria was met in 34 patients. Baseline characteristics: mean age 81 years, female 50%, mean weight 75 kg, BMI of 25, Caucasians 79% and mean ejection fraction 26%. Mean NT-ProBNP change from baseline was -68%. The first 30-day HF readmission was 14.7%. No patients were discharged on intravenous inotropes and no mortality reported. Conclusions SVC appears to lower first 30-day HF hospital readmissions in patients &gt 75 years old. It is well-tolerated among this population. Further, well-designed study was warranted.

Effects of Very Low (12/13mg) and Low Dose (24/26mg) Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide

Introduction Sacubitril/valsartan (S/V) has been shown to decrease N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels. Reduction of NT-proBNP is associated with lower morbidity and mortality rates. However, there is very little data with the effects of low dose S/V on NT-proBNP. Methodology This was a retrospective study conducted between October 2015 and January 2018 of patients who received either low dose or very low dose S/V. Patients were divided into 3 groups based on S/V dosing. Group 1 patients received very low dose, group 2 patients received very low dose titrated to low dose, and group 3 patients received low dose. The primary endpoint was the change in NT-proBNP levels between baseline and the most recent obtained value. Results A total of 293 patients were reviewed and 45 patients met inclusion criteria. Across all S/V dosing groups, there was a statistically significant reduction in NT-proBNP levels. The average days of therapy between NT-proBNP values were 108, 149, and 196 in group 1, 2, and 3, respectively. 71% of patients were on loop diuretics prior to S/V with an average furosemide equivalent dose of 73mg which decreased by 27% to 53mg after receiving S/V. Conclusion Low doses of S/V, including half of the lowest dose clinically available, appears to have substantial benefit in terms of NT-proBNP which can be seen within 3 to 6 months. Despite a reduction in loop diuretic dose, there was still a significant reduction in NT-proBNP which may be attributed to the natriuretic effect of S/V. Although reductions in NT-proBNP levels are associated with improvements in survival, these data cannot be used to infer that a similar reduction in mortality would be expected. However, they do suggest that very low doses of S/V appear to have a biochemical effect and perhaps should be studied in future trials since not all patients can be titrated to the maximum dose of S/V. While patients should be titrated to guideline recommended doses, low doses seem to be beneficial in terms of reducing NT-proBNP levels.

DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes

BackgroundUse of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD).MethodsB-type natriuretic peptide and NT-proBNP were measured using commercially available clinical-grade immune-assays at baseline and at the end of a 4-day treatment with placebo and linagliptin. Changes from baseline during each treatment arm, as well as placebo-subtracted effects of linagliptin on BNP and NT-proBNP were calculated.Results46 patients completed the study, 18 of whom were affected by CKD. Baseline BNP and NT-proBNP levels increased with age, were elevated in CKD patients, and inversely correlated with estimated glomerular filtration rate. No significant change was detected in BNP and NT-proBNP levels after treatment with linagliptin or placebo in patients with or without CKD. Only in CKD patients the placebo-subtracted effect of linagliptin indicated a significant reduction in NT-proBNP levels, but this finding was not statistically robust.ConclusionsAcute treatment with a DPP-4i exerts no clinically-meaningful effects on BNP and NT-proBNP. As routinely used immunoassays do not discriminate between intact/active and cleaved BNP, these data cannot rule out an effect of DPP-4i on HF pathophysiology.Trial registration NCT01617824

Abstract 15821: Safety and Efficacy of Non-invasive Ventilation During Exercise Training in Patients With Acute Heart Failure. A Randomized Prospective Controlled Study

Background: Exercise training (ET) is well established to improve functional capacity and quality of life in patients (pts) with chronic heart failure. However, the ET benefits in acute heart failure (AHF) are unknown. Purpose: We aimed to study the safety and efficacy of ET alone or combined with non-invasive ventilation (NIV) compared to standard medical treatment in hospitalized pts with AHF. Methods: Twenty-nine pts with AHF (68% ischemic), 56±7 years, left ventricle ejection fraction of 25±5%, NTproBNP of 2456±730, 6-minute walk test distance (6MWD = 225±39meters) were randomized into 3 groups: ET + NIV with sub therapeutic positive airway pressure (PAP) (ET,n=9), ET + NIV set to 14 of inspiratory and 8 cmH2O of expiratory PAP, respectively (EV,n=11) and standard treatment (CO,n=9). The ET and EV groups performed a daily session of unloaded exercise on cycle ergometer for 20 min or tolerance limit, for 8 consecutives days. In EV and ET, oxygen pulse saturation (SpO2), heart rate (HR), respiratory rate (RR), blood pressure (BP), blood lactate were measured at baseline (D1), during exercise, and at day 10 (D10). Serious adverse events (death or worsening heart failure) were also assessed on D10. Results: Length of hospital stay was shorter in EV group (17±10 days) compared to ET (23±8 days) and CO (39±15 days) (p&lt;0,05). There were more serious adverse events in CO (66,6%) compared to both EV and ET (15%). Dobutamine use at D10 was less frequent in EV (18,2%) and ET (22,2%) groups than in CO (33,3%) (p&lt;0.05). There was a marked improvement in Δ6MWD between D1 and D10 in EV (Δ127±72 meters), though increase in Δ6MWD was also seen in ET (Δ72±26 meters) and CO (Δ41±19meters), p&lt;0,05. The EV group also showed higher endurance and lower peak HR at end-exercise than ET at D10 (128±10 vs. 92±8 min and 73±12 vs. 104±25 bpm, respectively; p&lt;0,05). There was a similar reduction in NTproBNP levels but no differences were found in BP, SpO2, RR and blood lactate. Conclusion: Aerobic exercise in AHF was safe, reduced length of hospital stay and need for inotropics at D10. NIV + ET increased exercise endurance with lower cardiovascular stress.

ESC Congress 2015, London: hot lines truly hot?

ESC Congress 2015, London: hot lines truly hot?

178 Circulating Micrornas for Predicting and Monitoring Response to Mechanical Circulatory Support from a left Ventricular Assist Device

PurposeThere are few non-invasive techniques to predict and monitor patients’ responses to left ventricular assist device (LVAD) therapy. MicroRNAs (miRs) are small noncoding RNAs with intricate roles in cardiovascular disease....

Effect of atrioventricular optimization on circulating N‐terminal pro brain natriuretic peptide following cardiac resynchronization therapy

Following CRT, atrioventricular (AV) optimization is not routinely practised. To evaluate its clinical utility, we examined the effect of AV delay optimization on the prognostic biomarker NT-proBNP. We prospectively studied 72 patients (mean age 73 ± 12.5 years, 70.8% male, 55.6% ischaemic) undergoing iterative AV optimization. Patients were divided into those whose nominal setting appeared ideal and not changed (Group 1, n = 22) and those whose AV delay was optimized (Group 2, n = 50). All patients underwent NT-proBNP assessment prior to CRT, and pre- and a median 5 days post-optimization. Compared with Group 1, NT-proBNP fell significantly in Group 2 patients (median 474 pg/mL) following optimization (P = 0.00001). A significant change in filling pattern (defined as a change in AV delay >50 ms) was required in 30% of patients, and it was this subgroup that derived the greater reduction in NT-proBNP levels [-1407 pg/mL, interquartile range (IQR) -3042 to -346 pg/mL] compared with those requiring <50 ms AV delay change (-125 pg/mL, IQR -1038 to 6 pg/mL), P = 0.0011. The benefit of AV optimization was principally observed in reverse remodelling non-responders (median -2167 pg/mL, IQR -3042 to -305 pg/mL) and in patients with a pseudonormal or restrictive filling pattern (median -1407 pg/mL, IQR -2809 to -342 pg/mL), compared with those with more benign diastolic filling (median - 264 pg/mL, IQR -1038 to -21 pg/mL), P = 0.033. In one-third of patients, major filling pattern changes are achieved with AV optimization, associated with subsequent rapid falls in NT-proBNP. The greater the AV delay change, the larger the NT-proBNP fall, and non-responders and those with restrictive or pseudonormal filling despite CRT are most likely to benefit.

Impact of intracoronary reinfusion of bone marrow-derived mononuclear progenitor cells on cardiopulmonary exercise capacity in patients with chronic postinfarction heart failure

Intracoronary infusion of bone marrow-derived progenitor cells (BMC) in patients with chronic ischaemic heart failure (CHF) is associated with improvement in left ventricular ejection fraction (LVEF), reduction of NT-proBNP levels and improved prognosis. However, effects of this therapy on cardiopulmonary exercise capacity have not been investigated separately so far. One hundred and fifty-four patients with ischaemic heart failure (mean LVEF 40.3 ± 10.9 %, NT-proBNP 1,103 ± 1,436 pg/ml) underwent cardiopulmonary exercise capacity testing (CPX) before and 3 months after intracoronary infusion of autologous BMC. Thirty patients with a potential bias on the CPX course as concomitant coronary intervention, bypass surgery, new onset of arrhythmias or implantation of cardiac resynchronization devices were excluded from further analysis. The remaining 124 patients showed an increase in exercise time and peak workload by 16.8 and 6 %. Peak oxygen uptake and oxygen uptake efficiency slope also improved by 2.9 and 12.9 %, whereas other parameters like peak oxygen pulse and the slope of minute ventilation versus CO2 elimination remained unchanged. Analysis of patients with poor, moderate and conserved CPX results prior to cell therapy documented that patients in tertiles with lowest initial exercise capacity showed the largest improvements in CPX after therapy. The differences in response to cell therapy were detectable in all investigated CPX parameters and became significant for exercise time, peak oxygen uptake and peak oxygen pulse. These findings indicate that intracoronary BMC therapy improves exercise capacity in CHF patients with more advanced heart failure.

Levosimendan may provide a better neurohormonal response in heart failure patients receiving beta blocker therapy — Reply

The hemodynamic effects of levosimendan have been shown to be maintained or even enhanced by beta blockers. Furthermore, levosimendan has recently been reported to represent mortality benefit in patients receiving beta blockers. However, it is not clear whether these favorable effects of levosimendan under beta blockade are also suggested by a better neurohormonal response. We evaluated neurohormonal response to levosimendan in patients receiving beta blocker in our study population on the basis of the comments of Giamouzis and colleagues on previously published article, in which both levosimendan and dobutamine were found to be very effective inotropic agents in achieving favorable neurohormonal response but levosimendan had a better and prolonged effect. The findings of recent subgroup analysis suggested that levosimendan treatment trended toward a greater reduction in NT-proBNP levels and therefore may provide a better neurohormonal response in patients receiving beta blockers as compared with those patients not receiving beta blocker.

Natriuretic peptide-guided levosimendan therapy for heart failure: A promising new approach

We read with great interest the letter by Cavusoglu et al. demonstrating that in patients with acute decompensated heart failure (ADHF) levosimendan treatment leads to a significant reduction in NT-proBNP levels for at least up to 48 h [1]. These results are in concordance with previous studies [2–6]. Such a trend was not seen with dobutamine infusion. Considering the now well accepted prognostic importance of natriuretic peptide levels in patients with heart failure, it would have been of great interest if the investigators had measured the levels of NT-proBNP longitudinally over time for a longer duration to document the overall magnitude and duration of NT-proBNP suppression by a single 24-h levosimendan infusion. Moreover, a concomitant group of patients receiving only diuretic therapy would have further helped navigate the difficult and largely unanswered question of how to optimally manage patients with ADHF. Nevertheless, the investigators do provide important new insights into the neurohormonal modulation by levosimendan that raises important novel therapeutic questions. Of great interest is the fact that none of the patients were receiving treatment with a β-blocker agent prior to the administration of the study drug. Although from an ideal

Perindopril-based blood pressure-lowering therapy reduces amino-terminal-pro-B-type natriuretic peptide in individuals with cerebrovascular disease

The plasma amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) level predicted congestive heart failure, myocardial infarction, and ischaemic stroke in participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of the effects of blood pressure lowering on cardiovascular events among individuals with cerebrovascular disease. Active treatment comprised a flexible regimen based on perindopril, with the addition of indapamide at the discretion of treating physicians. Active treatment reduced cardiovascular events, and we therefore investigated whether active treatment modified NT-proBNP and other cardiovascular risk factors. We measured NT-proBNP and other cardiovascular risk factors at randomization and after 13 months of therapy in a subset of 357 PROGRESS participants. Baseline systolic and pulse pressures were higher in individuals with elevated baseline NT-proBNP levels. In comparison with placebo, active treatment reduced the blood pressure and NT-proBNP levels, and increased renin levels. Reduction of NT-proBNP levels by active treatment was most evident in individuals with baseline NT-proBNP levels in the highest quarter (> 26 pmol/l), with a median reduction of 16 pmol/l (interquartile range 0-51 pmol/l, P = 0.004), corresponding to a median decrease of 39% (interquartile range 0-69%). Active treatment reduced blood pressure similarly for individuals in each of the four quarters of baseline NT-proBNP. Active therapy had no effect on plasma lipid, C-reactive protein, homocysteine, or soluble vascular cell adhesion molecule 1 levels. We conclude that plasma NT-proBNP level, in addition to predicting cardiovascular risk, may provide a measure of risk reduction by blood pressure-lowering therapy.