Reduction In NT-proBNP Levels Research Articles

Baroreflex activation therapy in heart failure patients with reduced ejection fraction: a long-term follow up

Abstract Introduction Heart failure with reduced ejection fraction (HFrEF) is a major public health concern with substantial morbidity and mortality. Overactivation of the sympathetic nervous system is a key pathophysiological process driving heart failure progression. Baroreceptor activation therapy (BAT) targets this autonomic imbalance and is a promising treatment strategy for patients with HFrEF. Current short-term studies indicate that BAT provides symptomatic relief, improvement in left ventricular function and cardiac biomarkers. However, data regarding the long-term effect of BAT on HFrEF are scarce. Purpose This study aims to assess long-term outcome in HFrEF patients who underwent BAT. Methods Patients with HFrEF who received BAT between 2014-2023 were followed until latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow ups. Results 23 patients (mean age 66±10 years, 83% men) with HFrEF were included in the study. Etiology of heart failure was ischemic in 70%. The majority of patients (96%) suffered from NYHA III with a mean left ventricular ejection fraction (LVEF) of 23±8% and NTproBNP of 2463±2922pg/ml. Complication occurred in one patient during BAT implantation (4%). Mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1 year, of which 1 patient remained in ameliorated NYHA for 7.5 years. Evolution of NYHA functional class over time is shown in Figure 1. Echocardiographic evaluation revealed significant improvement in LVEF of 9±9% after 1 year (p<0.001) and by 11±9% after 2 years (p=0.005). In long-term a trend towards improved LVEF could be observed (Figure 2). In addition, BAT mildly reduced NTproBNP in the first 2 years (after 1 year non-significantly by -396±1006pg/ml and significantly after 2 years by -566±651pg/ml (p=0.039)). Seven patients reaching recommended replacement time underwent device exchange. Four patients deceased during observation time. Conclusion BAT resulted in a substantial reduction in NYHA classification, improvement in LVEF, and a delayed reduction in NTproBNP levels. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.Sankey plot of NYHA class over timeAlteration of LVEF over time

Semaglutide improves contractile function in isolated human atrium

Abstract Background Recently, the results of the STEP-HFpEF trial were announced, in which high-dose treatment with the antidiabetic glucagon-like-peptide 1 agonist semaglutide resulted in a significant improvement of HFpEF-associated symptoms and reduction of NT-proBNP levels. Interestingly, treatment effects were independent of initial body weight and left-ventricular ejection fraction, sparking interest regarding the precise mechanism of action. Purpose We tested the effects of acute semaglutide treatment in isolated human right-atrial trabeculae. Methods Trabeculae were prepared from right atrial appendage biopsies from 32 patients undergoing elective coronary artery bypass grafting and/or valve surgery. Regular contractions were elicited by electrical field stimulation (1Hz, 5V/50ms, 37°C). Paired experiments were performed simultaneously per patient with a control group and one exposed to semaglutide (100 or 300nM). Developed tension was analysed at steady state after 30 min. Arrhythmias were defined as deviations from baseline not arising from electrical stimulation. L-type calcium channel blockade was achieved with nifedipine (2µM) in some experiments. Rapid cooling contraction was elicited to assess sarcoplasmic reticulum Ca2+ content (RCC1) by rapidly superfusing the trabeculae with chilled solution (2°C). After a short rewarming period of 10s to 37°C, RCC was repeated to assess the Na+/Ca2+ exchanger function (RCC2). Statistical analysis was conducted using paired t-test or Wilcoxon test as appropriate (for 2 groups) and one-way ANOVA with test for trend (for >2 groups). Results Exposure to semaglutide increased developed tension by over 3-fold in human atrial trabeculae in a dose-dependent manner: from 3.14±1.14 for control to 5.43±2.35mN/mm2 for 100nM semaglutide (p=0.03 vs. control) to 12.5±3.53 for 300nM semaglutide (p=0.004 vs. control, mean±SEM, fig. A-D, p=0.005 for linear trend). L-type calcium channel blockade with nifedipine blunted developed tension overall but did not abolish the effect of semaglutide (fig. E, p=0.02). In contrast, the developed tensions upon RCC1 and RCC2 were increased by semaglutide (300nM) compared to control, while the ratio of RCC2:RCC1 was elevated by semaglutide, indicating both increased SR Ca2+ reuptake and less external Ca2+ removal in the presence of semaglutide (fig. H-J). Relaxation time to 50% of baseline was unaltered (not shown), while relaxation time to 90% of baseline was mildly prolonged by semaglutide at 300 nM (fig. F). No increase in the rate of arrhythmias was observed by semaglutide treatment (fig. G). Conclusion Acute exposure of human atrial trabeculae to semaglutide results in a strong positive inotropic effect in a dose-dependent manner without increasing the propensity for arrhythmias. This effect is most likely due to increased SR Ca2+ reuptake. Treatment of heart failure patients with high-dose semaglutide can improve atrial function, which may ameliorate symptoms.

Colchicine in acutely decompensated heart failure: the COLICA trial.

Acute heart failure (AHF) promotes inflammatory activation, which is associated with worse outcomes. Colchicine has proven effective in other cardiovascular conditions characterized by inflammatory activation, but has never been evaluated in the setting of AHF. This multicenter, randomized, double-blind and placebo-controlled trial included patients with AHF, requiring ≥40 mg of intravenous furosemide, regardless of their left ventricular ejection fraction (LVEF) and inpatient or outpatient setting. Patients were randomized within the first 24 hours of presentation to receive either colchicine or placebo, with loading dose of 2 mg followed by 0.5 mg every 12 hours for 8 weeks. A total of 278 patients (median age 75 years, LVEF 40%, baseline N-terminal pro-B-type natriuretic peptide [NT-proBNP] 4390 pg/mL) were randomized to colchicine (n=141) or placebo (n=137). The primary endpoint, the time-averaged reduction in NT-proBNP levels at 8 weeks, did not differ between the colchicine group (-62.2%, 95% confidence interval [CI] -68.9% to -54.2%) and the placebo group (-62.1%, 95% CI -68.6% to -54.3%) (ratio of change 1.0). The reduction in inflammatory markers was significantly greater with colchicine: ratio of change 0.60 (p<0.001) for C-reactive protein and 0.72 (p=0.019) for interleukin-6. No differences were found in new worsening heart failure episodes (14.9% with colchicine vs. 16.8% with placebo, p=0.698); however, the need for intravenous furosemide during follow-up was lower with colchicine (p=0.043). Diarrhea was slightly more common with colchicine, but it did not result in differences in medication withdrawal (8.5% vs. 8.8%). Colchicine was safe and effective in reducing inflammation in patients with AHF, however colchicine and placebo exhibited comparable effects on reducing NT-proBNP and preventing new worsening heart failure events.

Impact of the SGLT2-inhibitor empagliflozin on inflammatory biomarkers after acute myocardial infarction – a post-hoc analysis of the EMMY trial

BackgroundSGTL2-inhibitors are a cornerstone in the treatment of heart failure, but data on patients with acute myocardial infarction (AMI) is limited. The EMMY trial was the first to show a significant reduction in NTproBNP levels as well as improved cardiac structure and function in post-AMI patients treated with Empagliflozin compared to placebo. However, data on the potential impact of SGLT2-inhibitors on inflammatory biomarkers after AMI are scarce.Materials and methodsThe EMMY trial is an investigator-initiated, multicentre, double-blind, placebo-controlled trial, which enrolled patients after AMI, receiving either 10 mg Empagliflozin once daily or placebo over a period of 26 weeks on top of standard guideline-recommended therapy starting within 72 h after percutaneous coronary intervention. In this post-hoc subgroup analysis of the EMMY trial, we investigated inflammatory biomarkers of 374 patients. The endpoints investigated were the mean change in inflammatory biomarkers such as high-sensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), neutrophils, leukocytes, neutrophile/lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) from baseline to 26 weeks.ResultsBaseline median (interquartile ranges) IL-6 was 17.9 pg/mL (9.0-38.7), hsCRP 18.9 mg/L (11.2–37.1), neutrophil count 7.9 x G/L (6.2–10.1), leukocyte count 10.8 x G/L (9.1–12.8) and neutrophile/lymphocyte ratio (NLR) of 0.74 (0.67–0.80). At week 26, a significant mean reduction in inflammatory biomarkers was observed, being 35.1 ± 3.2% (p < 0.001) for IL-6, 57.4 ± 0.7% (p < 0.001) for hsCRP, 26.1 ± 0.7% (p < 0.001) for neutrophils, 20.5 ± 0.6% (p < 0.001) for leukocytes, 10.22 ± 0.50% (p < 0.001) for NLR, and − 2.53 ± 0.92% for PLR (p = 0.006) with no significant difference between Empagliflozin and placebo treatment.ConclusionTrajectories of inflammatory biomarkers showed a pronounced decline after AMI, but Empagliflozin treatment did not impact this decline indicating no central role in blunted systemic inflammation mediating beneficial effects.

THE CARDIOPROTECTIVE EFFECTS OF EMPAGLIFLOZIN IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION AND TYPE 2 DIABETES MELLITUS

Introduction. Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome associated with significant morbidity and mortality. Type 2 diabetes mellitus (T2DM) often coexists in patients with HFpEF, further exacerbating the cardiovascular risk. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, has shown promising results in improving cardiovascular outcomes in patients with T2DM. However, the specific cardioprotective effects of empagliflozin in patients with HFpEF and T2DM remain to be elucidated.&#x0D; Aim. To assess the effect of empagliflozin on biochemical markers of heart failure in patients with type 2 diabetes mellitus and heart failure with preserved ejection fraction.&#x0D; Materials and Methods. The study included 80 patients with HFpEF and T2DM, with 40 patients in the empagliflozin group and 40 patients in the control group. Baseline characteristics, including age, gender, blood pressure, body mass index, and cardiac markers (HbA1c, NT-proBNP, Galectin-3, and sST2), were assessed. Changes in glycemic control and cardiac markers were analyzed after the treatment period.&#x0D; Results. Baseline characteristics showed no significant differences between the two groups, indicating successful randomization. Post-treatment analysis revealed a numerical trend towards improved glycemic control in the empagliflozin group compared to the control group. Notably, empagliflozin treatment led to a significant reduction in NT-proBNP levels, indicating improved cardiac function and reduced cardiac stress. Furthermore, empagliflozin was associated with lower Galectin-3 and sST2 levels, suggesting potential benefits in mitigating cardiac fibrosis, remodeling, and inflammation.&#x0D; Conclusions. Empagliflozin treatment in patients with HFpEF and T2DM have multifaceted implications beyond glycemic control. The observed reductions in NT-proBNP, Galectin-3, and sST2 levels suggest potential improvements in cardiac function, fibrosis, remodeling, and inflammatory processes. These findings highlight the potential of empagliflozin as a therapeutic option for managing HFpEF and T2DM, offering the potential for comprehensive cardiovascular benefits in this patient population.

Short-term Changes in Hemoglobin and Changes in Functional Status, Quality of Life and Natriuretic Peptides After Initiation of Dapagliflozin in Heart Failure With Reduced Ejection Fraction

We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels. This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO2) (NCT04197635). This substudy evaluated 1- and 3-month changes in hemoglobin levels and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ) and NT-proBNP levels. At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month: + 0.45 g/dL (P = 0.037) and 3 months:+ 0.55 g/dL (P = 0.012)]. Changes in hemoglobin levels positively mediated the changes in peak VO2 at 3 months (59.5%; P < 0.001). Changes in hemoglobin levels significantly mediated the effect of dapagliflozin in the MLHFQ at 3 months (-53.2% and -48.7%; P = 0.017) and NT-proBNP levels at 1 and 3 months (-68.0%; P = 0.048 and -62.7%; P = 0.029, respectively). In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.

Levosimendan in outpatients with advanced heart failure: Single-center experience of 200 intermittent perfusions

IntroductionPatients with advanced heart failure (HF) have high morbidity and mortality, with only a small proportion being eligible for advanced therapies. Intermittent outpatient levosimendan infusion has been shown to provide symptomatic relief and reduce the rate of HF events. Our aim was to assess the safety and efficacy of outpatient levosimendan administration in an advanced HF population. MethodsThis is a report of a single-center experience of consecutive advanced HF patients referred for intermittent intravenous outpatient administration of levosimendan, between January 2018 and March 2021. Baseline and follow-up evaluation included clinical assessment, laboratory tests, transthoracic echocardiography and cardiopulmonary exercise testing. Baseline and clinical follow-up data were compared using the Wilcoxon signed-rank test. ResultsA total of 24 patients (60.8 years, 83% male, mean left ventricular ejection fraction [LVEF] 24%), with a median of 1.5 HF hospitalizations in the previous six months, were referred for outpatient levosimendan pulses, the majority as a bridge to transplantation or due to clinical deterioration. At six-month follow-up there was a significant reduction in HF hospitalizations to 0.4±0.7 (p<0.001). NYHA class IV (52.2% to 12.5%, p=0.025) and NT-proBNP (8812.5 to 3807.4 pg/ml, p=0.038) were also significantly reduced. Exercise capacity was significantly improved, including peak oxygen uptake (p=0.043) and VE/VCO2 slope (p=0.040). LVEF improved from 24.0% to 29.7% (p=0.008). No serious adverse events were reported. ConclusionRepeated levosimendan administration in advanced HF patients is a safe procedure and was associated with a reduction in HF hospitalizations, functional and LVEF improvement, and reduction in NT-proBNP levels during follow-up.

Early Administration of Sacubitril/Valsartan is Associated with more Rapid NT-proBNP Recovery in High-Risk Patients Hospitalized for Acute Heart Failure

BACKGROUND: in patients hospitalized for heart failure with reduced ejection fraction (HFrEF), randomized controlled trials have demonstrated some advantages in starting sacubitril/valsartan before discharge. However, information about the effects of sacubitril/valsartan use in the acute phase of HfrEF hospitalizations is limited. AIM: To evaluate clinical, biomarker, and echocardiographic effects of starting sacubitril/valsartan in real-world HFrEF patients before discharge. METHODS: retrospective analysis of 124 consecutive patients (58.9% males, 75.6±11.4 years) hospitalized for HFrEF. In 36, sacubitril/valsartan was started before discharge (Group A); in the remaining 88, at the 1-month follow-up visit (Group B). The primary endpoint was time-averaged NT-proBNP level reduction from admission to discharge. RESULTS: Group A showed a worse baseline clinical risk profile (diabetes: 47.2 vs. 20.7%, p=0.007; coronary artery disease: 66.7 vs. 22.7%, p&lt;0.001; systolic blood pressure: 118.0±20.8 vs. 132.9±22.9 mmHg, p=0.001; left ventricular ejection fraction: 28.5±5.5 vs. 32.1±7.6%, p&lt;0.0004). Nevertheless, the time-averaged mean NT-proBNP reduction was significantly higher in group A patients (ratio of change -0.30, 95% CI -0.40 to -0.21, &lt;0.0001 vs. group B). Creatinine and K+ levels did not change significantly during the hospital stay. Multivariate analysis suggested diabetes, coronary artery disease, higher systolic blood pressure, and the need for inotropic support as independent predictors for in-hospital sacubitril/valsartan treatment. CONCLUSIONS: in real-world patients, starting sacubitril/valsartan in-hospital rather than waiting for further stabilization was associated with a more considerable reduction of NT-proBNP levels at discharge, with an excellent safety profile. These data confirm randomized trials results, extending them to higher-risk real-world HFrEF patients.

Haemodynamic forces as predictors of cardiac remodelling and outcome in heart failure with reduced ejection fraction treated with sacubitril/valsartan

Abstract Background Angiotensin receptor-neprilysin inhibitor (ARNI) is a cornerstone of treatment in heart failure (HF) with reduced ejection fraction (HFrEF), but its effectiveness shows interindividual differences. Objectives To evaluate the predictive value of echo-derived hemodynamic forces (HDF), together with other echocardiographic, biohumoral and cardiopulmonary parameters on a) response to ARNI after 6 months; b) adverse cardiovascular events at follow-up. Methods Eighty-nine consecutive HFrEF patients from two HF centers performed clinical evaluation, laboratory analyses, rest echocardiography and cardiopulmonary exercise testing. Response to ARNI at 6 months was considered in patients without HF admissions, death, or urgent heart transplant and with a ≥50% reduction in NT-proBNP levels and/or ≥10% increase in left ventricle ejection fraction. After 6 months, patients were followed up for a composite endpoint of cardiovascular death, HF-related hospitalization and new-onset atrial fibrillation. Results Response to ARNI was documented in 45/89 (51%) of patients. At baseline, responders and non-responders were paired in clinical assessment, conventional echocardiography, functional status and therapy. At multivariate logistic regression analysis, HDF-derived whole cardiac cycle left ventricle strength (wLVS) was the only independent predictor of ARNI response at 6 months (odds ratio 1.36, 95% confidence interval 1.10–1.67; p=0.004). A wLVS ≥3.7% showed a good accuracy in predicting ARNI response (AUC = 0.736, 0.607–0.840; p&amp;lt;0.0001). During a median of 33 (IQR 23–41) months, wLVS increase from baseline to 6-month (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≤0.5%; AUC=0.811, 0.69–0.90; p&amp;lt;0.0001), stratified prognosis at Kaplan-Meier analysis (log-rank p&amp;lt;0.0001), and remained an independent prognostic predictor of the composite endpoint (hazard ratio 0.76, 0.61–0.95; p&amp;lt;0.01) even after adjusting for clinical, functional and conventional echocardiographic parameters. Conclusions HDF analysis may help predict ARNI response and optimize follow-up and medical/device strategies in patients with HfrEF. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Fondazione Toscana Gabriele Monasterio, Pisa, Italy

Association of Repetitive Dosing of Levosimendan with Reduction of NYHA Class and NT-proBNP Levels in Decompensated Heart Failure: A Retrospective Cohort Study.

BackgroundThere is evidence that repetitive administration of levosimendan can improve outcome in chronic heart failure patients.ObjectiveThe aim of this retrospective study was to investigate the effect of therapy with levosimendan (LEV) additional to standard medical care in patients with symptomatic heart failure (HFrEF = heart failure with reduced ejection fraction) on NYHA class, NT-proBNP values, ejection fraction (EF) and body weight.Patients and Methods178 participating patients (125 male, 53 female; mean age of 73 ± 13 years) were grouped according to whether LEV was given once (group 1) or repetitively (group 2). In group 2 data were analysed for first treatment with LEV (group 2a) and for the following repetitive LEV treatments (group 2b). The differentiation was required to see if there were different results for the particular groups.ResultsRepetitive dosing was given between two and 11 times, leading to 47 repetitive applications of LEV and a total of 225 (178 once + 47 repetitive) applications. The mean time between the repetitive dosing was 133 days or 4.3 months. LEV in addition to standard medical treatment was associated with reduction of NT-proBNP levels from 9138 to 7051 pg/mL (p < 0.05). The corresponding values in group 2a and group 2b were 8790–4717 pg/mL (p < 0.05) as well as 13,681–7581 pg/mL (p < 0.05). The ejection fraction measured by echocardiography improved from 30 to 38% in group 1, from 31 to 45% in group 2a and from 30 to 35% in group 2b (p < 0.05). Addition of LEV was associated with significant reduction of NYHA class and bodyweight in all groups. No adverse side effects (e.g., rhythm disorder, hypotension, electrolyte disorder) were seen.ConclusionLEV may be useful as an additive to standard care of treatment for patients with acute de novo decompensation due to acute heart failure as well as to prevent further deterioration in patients with chronic heart failure disease at high risk for hospitalisation. Intraindividual changes in NT-proBNP levels may be useful in decision-making about the need for additional treatment options in patients with worsening heart failure.

Dapagliflozin Impact on the Exercise Capacity of Non-Diabetic Heart Failure with Reduced Ejection Fraction Patients.

Background: Dapagliflozin has been shown to reduce morbidity and mortality in Heart Failure with reduced Ejection Fraction (HFrEF), but its impact on exercise capacity of non-diabetic HF outpatients is unknown. Methods: Adult non-diabetic HF patients with a left ventricular ejection fraction (LVEF) <50% were randomized 1:1 to receive dapagliflozin 10 mg or to continue with HF medication. Patients underwent an initial evaluation which was repeated after 6 months. The variation of several clinical parameters was compared, with the primary endpoint being the 6 month peak oxygen uptake (pVO2) variation. Results: A total of 40 patients were included (mean age 61 ± 13 years, 82.5% male, mean LVEF 34 ± 5%), half being randomized to dapagliflozin, with no significant baseline differences between groups. The reported drug compliance was 100%, with no major safety events. No statistically significant difference in HF events was found (p = 0.609). There was a 24% reduction in the number of patients in New York Heart Association (NYHA) class III in the treatment group as opposed to a 15.8% increase in the control group (p = 0.004). Patients under dapagliflozin had a greater improvement in pVO2 (3.1 vs. 0.1 mL/kg/min, p = 0.030) and a greater reduction in NT-proBNP levels (−217.6 vs. 650.3 pg/mL, p = 0.007). Conclusion: Dapagliflozin was associated with a significant improvement in cardiopulmonary fitness at 6 months follow-up in non-diabetic HFrEF patients.

Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study.

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) <35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e’ ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.

EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS THERAPY ON LEFT VENTRICULAR HYPERTOPHY AND NT-PROBNP LEVEL IN HYPERTENSIVES

Objective: To evaluate the effect of valsartan, eprosartan or losartan on LVH and NT-proBNP levels in patients with hypertension and preserved ejection fraction Design and method: This is randomized, prospective and double-blind study involved 154 hypertensive patients (56,5% men; mean age 53,6 ± 0,5 years) with concentric LVH remodeling (LV mass &gt; 115 g/m2 and 95 g/m2 in men and women, respectively), which were eligible criterions to randomize to receive medication into three groups: valsartan (n = 48), eprosartan (n = 54), losartan (n = 52) over a follow-up period of 24 months. Echocardiography, ambulatory blood pressure monitoring and NT-proBNP assessments were performed at baseline and after 24 months treatment. Results: Despite similar effects on ambulatory blood pressure levels, significant differences on LV mass index were found between valsartan, eprosartan and losartan treatment (mean decrease 27.0 g/m2 vs 35 g/m2 and 24.0 g/m2, respectively, p &lt; 0,001), and there was positive correlation of changes in ambulatory systolic blood pressure with LV mass index (r = 0,5; p &lt; 0,001). Eprosartan-based therapy induced a greater reduction in NT-proBNP levels (-45,6%, p &lt; 0,001) from baseline than in the valsartan (-28,9%, p &lt; 0,01) and losartan group (- 26,5%,, p &lt; 0,01). Conclusions: The findings of this study showed that all three agents progressively reduced LVH, but the reduction was significantly greater in the eprosartan group. Additionally, eprosartan was associated with a greater reduction of NT-proBNP levels.

A Simple Score to Identify Super-Responders to Sacubitril/Valsartan in Ambulatory Patients With Heart Failure.

IntroductionSacubitril/valsartan (SV) promotes cardiac remodeling and improves prognosis in patients with heart failure (HF). However, the response to the drug may vary between patients and its implementation in daily clinical practice has been slower than expected. Our objective was to develop a score predicting the super-response to SV in HF outpatients.MethodsThis is a retrospective analysis of 185 consecutive patients prescribed SV from two tertiary hospitals between September 2016 and February 2018. Super-responder was defined as a patient taking the drug and (i) without HF admissions, death, or heart transplant, and (ii) with a ≥50% reduction in NT-proBNP levels and/or an increase of ≥10 points in LVEF in a 12-month follow-up period after starting SV. Clinical, echocardiographic, ECG, and biochemical variables were used in a logistic regression analysis to construct a score for super-response to SV which was internally validated using bootstrap method.ResultsOut of 185 patients, 65 (35%) fulfilled the super-responder criteria. Predictors for super-response to SV were absence of both previous aldosterone antagonist and diuretic treatment, NYHA I-II class, female gender, previous 1-year HF admission, and sinus rhythm. An integrating score distinguished a low- (<25%), intermediate- (∼46%), and high-probability (>80%) for 1-year super-response to SV. The AUC for the model was 0.72 (95%CI: 0.64–0.80), remaining consistent after internal validation.ConclusionOne-third of our patients presented a super-response to SV. We propose an easy-to-calculate score to predict super-response to SV after 1-year initiation based on variables that are currently assessed in clinical practice.

A clinical experience of Indian patients with heart failure with reduced left ventricular ejection fraction using an angiotensin receptor-neprilysin inhibitor [ARNI] on an outpatient basis

The goal of this study is to portray an initial experience with the efficacy, safety, and, acceptance of ARNI in ambulatory cardiology practices in India. The research is a retrospective review of single-centre data who began therapy with ARNI in HFrEF between 2019 and 2020. The analysis included data for 454 symptomatic patients, aged 57 ± 20.8 years in NYHA class II-III. During follow-up, patients experienced significant improvement in HF symptoms determined by using Kansas City Cardiomyopathy Questionnaire (KCCQ) and a considerable reduction in NT-proBNP levels. ARNI is associated with substantial clinical benefit in an outpatient setting in HFrEF.

The Effect of Sacubitril/Valsartan in a Dialysis Patient with Severe Heart Failure

Heart failure (HF) is a major comorbidity in patients with end-stage renal disease (ESRD). The pathogenesis of HF in patients on renal replacement therapy represents the confluence of several traditional and nontraditional vascular risk factors, unique to the milieu of chronic kidney disease and the dialysis modality [1]. The purpose of this report is to describe the efficacy and safety of sacubitril/valsartan for an ESRD patient on hemodialysis therapy conmbined with heart failure with reduced ejection fraction (HFrEF). A 35-year-old woman was undergoing hemodialysis due to ESRD and suffering from heart failure with reduced ejection fraction. Because of worsening heart failure and hypertension, she was prescribed with sacubitril/valsartan at a dose of 50 mg twice a day, spironolactone at a dose of 20 mg three times a day and metoprolol at a dose of 23.75 mg once daily. There was a symptomatic improvement with the heart failure and reduction in NT-proBNP level, accompanied by a decrease of blood pressure after using sacubitric/valsartan. In conclusion, it is safe and effective to take sacubitril/valsartan in this hemodialysis patient with severe heart failure.

Use of Sacubitril/valsartan in patients with cardio toxicity and heart failure due to chemotherapy

BackgroundCancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. Standard therapy for heart failure (HF) is recommended for CTRCD, but there is no well-established evidence on how sacubitril/valsartan may help cancer patients with cardiotoxicity.ObjectivesThe aim of this trial was to study the effectiveness of sacubitril-valsartan in patients with CTRCD treated in cardio-oncology units.MethodsWe enrolled 635 patients with breast cancer and followed them with echocardiography and NT- proBNP. Patients who developed left ventricular dysfunction and heart failure were treated with angiotensin-converting enzyme inhibitors (ACEI) (enalapril) or angiotensin receptor blockers (ARB) (valsartan), aldosterone antagonists (eplerenone), digitalis and diuretics (furosemide), as needed. When patients remained symptomatic and met the PARADIGM-HF inclusion criteria, sacubitril/valsartan was started instead of enalapril or valsartan.We analyzed clinical, laboratory and echocardiographic variables to determine the beneficial effects of sacubitril/valsartan on left ventricular remodeling (improvement of left ventricular ejection fraction (LVEF), left ventricle internal diameter in diastole), diastolic dysfunction (E/e’ ratio), reduction in NT-proBNP levels, New York Heart Association (NHYA) class and improvement in the 6-min walk test.Also, we analyzed serum creatinine and potassium levels to determine treatmentsafety in this population. Median follow-up was 20 months.ResultsTwenty-eight patients developed cardiotoxicity and were treated with sacubitril/valsartan. The sacubitril/valsartan dose was 100 mg (sacubitril 49 mg/valsartan 51 mg) in 12 patients (42.85%) and 200 mg (sacubitril 97 mg/valsartan 103 mg) in 16 patients (57.15%). No deaths were reported, and one patient underwent heart transplantation.Baseline median NT-proBNP was 997.5 pg/ml (IQR 663.8 — 2380.8), which decreased to a median of 416.5 pg/ml (IQR 192.0–798.2) on follow-up with p < 0.001.Baseline NYHA functional class was III (78.6%) or IV (21.4%), and it improved to I (57.1%) or II (42.9%) on follow-up. LVEF increased with treatment from 26.7 ± 5.4% to 32.3 ± 5.5% (p < 0.001). There were also significant improvements in left ventricle internal diameter in diastole (LVIDD), diastolic function, 6-min walk test, and mitral valve regurgitation. There were no differences between basal and follow-up levels of serum creatinine or potassium.ConclusionSacubitril/valsartan might be a promising treatment option in patients with refractory CTRCD.

Feasibility and rationale of direct current cardioversion immediately after transcatheter percutaneous edge-to-edge mitral valve repair.

Atrial fibrillation (AF) is a frequent comorbidity among patients with severe mitral regurgitation (MR). Direct current (DC) cardioversion is one of the strategies for rhythm control. However, the safety and feasibility of immediate DC cardioversion after MitraClip are not elucidated. In this study, patients with symptomatic severe MR who underwent MitraClip were included. After fixing the MR, synchronized DC cardioversion was attempted for those with AF. A total of consecutive 60 patients, 36 subjects (60%), comorbid with AF. DC cardioversion was performed in 30 patients (mean age of 76.0±9.3years), and the successful conversion was achieved in 15 patients (50%). There was no any adverse event related to the cardioversion. Subjects with sustained conversion to SR experienced significant improvement in 6MWT (failed: 285±110-308±135m, P=.278; successful: 269±109m-328±78, P=.047) and reduction in NT-proBNP level (failed: 4411±7401-3296±4299ng/mL, P=.217; successful: 4094±2735-2353±2856ng/mL, P=.026) at 1month. Direct current cardioversion seemed to be safe and feasible immediately after the transcatheter edge-to-edge mitral valve repairs. Subjects who maintain SR experienced better functional improvement.

P0244OVERTURNING THE CONVENTIONAL PYRAMID OF AL AMYLOIDOSIS MANAGEMENT: DARATUMUMAB ADMINISTERED AS MONOTHERAPY IN SEVERE PATIENTS WITH BIOPSY PROVEN RENAL INVOLVEMENT

Abstract Background and Aims Immunoglobulin light chain amyloidosis (AL) with multi-organ involvement is characterized by poor outcome. Current treatment of AL targeting the underlying plasma cell clone has been adapted from the multiple myeloma (MM). Novel powerful drugs are expanding the therapeutic options. Daratumumab is a first-in-class anti-CD38 human antibody (IgG1κ) which proved to be effective in combination with bortezomib in MM refractory to conventional bortezomib-based regimens. Its effectiveness as a single agent and its safety in the treatment of AL amyloidosis is under study. Aim of the study: This study reports the experience with Daratumumab monotherapy in a series of severe patients with AL amyloidosis and multiorgan and biopsy-proven renal involvement. Method Five patients (2 males and 3 females), mean age 64 years (range 52-69) were treated with Daratumumab following antibody testing and extended RBC antigen phenotyping. Treatment protocol was as follows: 16 mg/kg Daratumumab i.v. administered weekly for 8 weeks, then 8 times every two weeks, and then monthly for 1 year. Premedication included oral paracetamol, and i.v. chlorphenamine and methylprednisolone. Results In patient #1, in dialysis, who was refractory to conventional therapies Daratumumab administration resulted in normalization of the FLC ratio with disappearance of serum M-component and Bence-Jones (BJ) proteinuria. In patient #2 who had a relapsing disease, Daratumumab treatment resulted in a rapid decrease of proteinuria (from 6.8 to 2.7gr/24 hours at the 16th dose) and N-terminal propeptide (NT-pro-BNP) levels (from 1844 pg/ml to 330 pg/ml) with disappearance of serum M-component and BJ proteinuria and normalization of the FLC ratio. Patient #3 was treated front-line. He had an impressive decrease of proteinuria from 9.3 to 2.2 gr/24 hrs and NT-proBNP levels (from 850 pg/ml to 225 pg/ml) with normalization of FLC ratio and disappearance of serum M-component. In patient #4, who was intolerant to conventional regimens, Daratumumab therapy resulted in decrease in proteinuria, disappearance of serum M-component and improvement in the FLC ratio, which were paralleled by a reduction of NT-proBNP levels. Patient #5 had a relapsing disease. Daratumumab achieved a decrease of proteinuria (from 2.5 to 1 gr/24 hrs9, a decrease of serum M-component with increase of FLC ratio (0.29, nv: 0.31 – 1.56). This was the only patient who experienced an infusion reaction during the first dose (grade 1). The 4 patients with still preserved renal function also showed renal response with sCr improvement or stabilization and a decrease in proteinuria levels These data were paralleled by the reduction of NT-proBNP values in the 3 patients with cardiac involvement. Conclusion Daratumumab monotherapy resulted in the disappearance of M-proteins in every patient with FLC ratio normalization in 4 out of 5 subjects and impressive decrease of proteinuria and pro-BNP values proving to be an effective therapeutic option for pretreated/naïve patients with severe AL with renal involvement.

Usefulness of Peritoneal Ultrafiltration in Patients with Diuretic Resistant Heart Failure without End-Stage Renal Disease

Aim: This study aimed to explore the role of peritoneal ultrafiltration (UF) in cardiorenal syndrome (CRS) patients for fluid and metabolic control. Background: Peritoneal UF is safely and efficiently used for the management of CRS. It has been shown to provide efficient UF in hypervolemic patients. Methods: Thirty (20 males and 10 females) CRS patients were treated by peritoneal dialysis (PD) and UF. The baseline data of the patients (demographics, causes of heart failure, the presence of pacemaker or implantable cardioverter-defibrillator, the need for extracorporeal UF or paracentesis or thoracentesis, comorbidity, drugs, left ventricular ejection fraction [LVEF] and pulmonary artery systolic pressure [PAPs], pericardial effusion, physical examination, body weight, NYHA class, dialysis regime, urine output, N-terminal pro-B-type natriuretic peptide [NT-proBNP] level, hemoglobin, estimated glomerular filtration rate [eGFR], and other routine biochemical determinations) were recorded at the onset, every 6 months, and then annually. Echocardiograms were performed at baseline and after 6 and 12 months. The time points of complications associated with PD, the need for hemodialysis, the day of death, and causes of death were documented. Results: Mean age was 69 ± 8 years (range 49–84 years). The average PD duration was 18.25 ± 14.87 months. According to the CKD-EPI, initial mean GFR was 34.34 ± 11.9 mL/min/1.73 m² (range 16.57–59.0), and this increased to 45.48 ± 26.04, 45.10 ± 28.58, and 41.10 ± 25.68 mL/min/1.73 m² in the third, sixth, and twelfth months, respectively. There was a significant increase in the first 3 months and a significant decrease between the third and twelfth months (respectively, p = 0.018 and p = 0.043). There was no difference in eGFR levels between baseline and the end of the first year (p = 0.217). In the first 3 months, there was a significant decline in urea levels to 79.38 ± 36.65 from 109.92 ± 42.44 mg/dL and this was maintained until the end of the first year of PD therapy (after 3 months, p = 0.002; after 1 year, p = 0.024). However, there was no significant change in creatinine levels within the first year (p = 0.312). There was a significant increase in hemoglobin level up to the end of the first year of PD (after 3 months, p = 0.000; after 12 months, p = 0.013). There was a marked decrease in NT-proBNP levels in the first 6 months (p = 0.011). Functional capacity (according to NYHA classification) improved in all patients by the third month of PD treatment (p < 0.001). This early improvement was maintained in many patients during the following 12 months (p < 0.001). There was a marked decrease in NT-proBNP levels in the first 6 months (p = 0.011). At the end of the first year, there was an approximate 15% reduction in NT-proBNP levels (p = 0.647). Hospitalizations decreased to 6 ± 15 days/patient-year (range 18–122 days) from 62 ± 24 days/patient-year (p = 0.000). Conclusion: Peritoneal UF is a treatment method that maintains renal function and electrolyte balance, improves cardiac function, and reduces hospitalizations in CRS patients. We observed that this treatment significantly increased functional capacity and quality of life and significantly reduced hospital admissions.