Changes In NT-proBNP Research Articles

Randomized trial of early exercise rehabilitation and its effects on patients with acute coronary syndrome

To assess the psychological and physiological benefits of early exercise rehabilitation in patients with acute coronary syndrome (ACS). Among 559 ACS-diagnosed patients at Fuzhou University Affiliated Provincial Hospital from January to December 2021, 200 eligible participants were assigned to two groups. The control group received standard care, while the experimental group received early exercise rehabilitation in addition to standard care. The outcomes measured included changes in depression levels (PHQ-9), fasting blood glucose, and troponin I (TnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Data were analyzed using SPSS, with t tests and chi-square tests for group comparisons. In comparison to the control group, the experimental group demonstrated significant improvements in PHQ-9 scores (P < 0.001) and lower fasting blood glucose levels before discharge (P = 0.046). Additionally, the experimental group had notably reduced TnI levels at 72 h after admission (P = 0.001), especially among non-diabetic NSTEMI patients over 60 years old, who showed decreased TnI levels at the 48-hour mark (P = 0.016). However, there were no significant differences in NT-ProBNP change values between the two groups (P > 0.05). Subgroup analysis revealed enhanced outcomes in the intervention group for ACS patients without smoking or drinking history and no heart failure (P = 0.025,P = 0.014,P = 0.018). Early exercise rehabilitation has notable benefits for ACS patients, including reduced depression, improved blood glucose control, and enhanced myocardial protection, especially in nondiabetic NSTEMI patients aged 60 and above.

Efficacy and safety of dapagliflozin in non-diabetic patients with primary anterior ST-elevation myocardial infarction initiated in early hospital period

Abstract Background The effectiveness of SGLT2 inhibitors has been proven in all types of chronic heart failure (HFpEF, HFmrEF, and HFrEF), regardless of the presence of diabetes mellitus. There are still no clear recommendations regarding the timing of SGLT2 inhibitor administration after myocardial infarction (MI) and its influence on prognosis. It can be assumed that it is appropriate to consider the possibility that, if started quickly after the presentation of acute MI, SGLT inhibition might enhance outcomes in patients. Objective This study aims to investigate the efficacy and safety of the SGLT2 inhibitor Dapagliflozin in primary anterior ST-segment elevation myocardial infarction (STEMI) initiated in early hospital period, irrespective of heart failure manifestation. Methods The study includes 124 non-diabetic patients with primary anterior STEMI who underwent primary PCI and had left ventricular ejection fraction (LV EF) ≤45% and NT-proBNP &amp;gt; 900 pg/ml at symptom onset within 24 hours, regardless of heart failure symptom manifestation. Patients with cardiogenic shock were excluded. 62 patients received standard medical treatment including beta-blockers, ACE inhibitors (Control group), while the other 62 patients were administered the SGLT2 inhibitor Dapagliflozin 10 mg once a day during the first 48 hours of inpatient treatment, in addition to standard therapy (Dapa group). All patients were followed up for one year. Echocardiography was performed during the first 24 hours. Echocardiography and NT-proBNP were repeated at the end of the year. The primary endpoint was the one-year heart failure hospitalizations and secondary endpoints included one year cardiovascular mortality and changes in NT-proBNP, plasma creatinine and glycosylated hemoglobin levels. Results The study shows a significant difference in heart failure hospitalization between the groups. In the Control group, it was 25.8%, and in the Dapa group, it was 8.1% (p = 0.008). Initially, there were no significant changes in NT-proBNP levels; 1152.2 ± 222.4 pg/ml in the Control group and 1197.3 ± 279.8 pg/ml in the Dapa group (p= 0.33). At the end of a year, NT-proBNP increased in the Control group (1827.4 ± 317.8 pg/ml), whereas in the Dapa group, it significantly decreased (613.5 ± 215.6 pg/ml) (p &amp;lt; 0.01). One-year cardiovascular mortality in the Control and Dapa groups was 9.7% and 4.8%, respectively(p=0.491). Other blood markers did not differ, and side effects were comparable during the in-hospital period as well as at the end of the year. Conclusion Early administration of Dapagliflozin among non-diabetic patients with primary anterior STEMI is associated with a significant decreasing of heart failure hospitalization rate and NT-proBNP level. Additionally, early administration of dapagliflozin does not impact on safety indicators.

Changes in N-terminal pro b-type natriuretic peptide according to SGLT2 inhibitor utilization patterns in patients hospitalized for decompensated heart failure: a prospective cohort study

Abstract Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors have found success in treating patients with chronic heart failure (HF) across the entire spectrum of left ventricular ejection fraction (EF). Their benefits may also extend to patients with acute HF decompensation, as they may aid effective decongestion. Purpose This study aims to present the various patterns in changes of N-terminal pro b-type natriuretic peptide (NT-proBNP) according to SGLT2 inhibitor use in patients hospitalized for acute HF decompensation. Methods In this prospective cohort study, we enrolled consecutive patients hospitalized for HF decompensation during a 4-month period in a cardiology department. Prior medical history and cardiovascular risk factors were recorded. The patterns in SGLT2 inhibitor use were noted and patients were classified into three groups; Group 1 (No SGLT2 inhibitor use/Discontinuation), Group 2 (Prior SGLT2 inhibitor use and continuation), and Group 2 (SGLT2i-naïve and initiation). Categorization according to left ventricular (EF) to HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF) was also performed. Moreover, estimated glomerular filtration rate (eGFR) was used as an estimate of renal function. Results In this analysis, 159 patients were included (median age: 79 years old, male sex: 64.8%, median duration of hospitalization: 6 days). In this population, 67.9% of the patients were not receiving a SGLT2 inhibitor on admission. Concerning demographic and clinical variables (Figure 1), there were no major differences in age, sex distribution, history of diabetes mellitus, dyslipidemia, and atrial fibrillation, as well as in renal function. Group 2 patients had a lower prevalence of arterial hypertension compared to Group 3 (36.6% vs. 52.6%, p&amp;lt;0.05). Moving to the changes in NTproBNP (Figure 2), we observed that patients who did not use SGLT2 inhibitors and did not initiate them during hospitalization had negligible changes in NTproBNP, either as an absolute change (Group 1: 506 (8792) pg/ml vs. Group 2: -5610 (9461) pg/ml vs. Group 3: -3602 (4409) pg/ml, p=0.001) or as percentage change (Group 1: -2.1 (63.4) % vs. Group 2: -30.3 (39.0) % vs. Group 3: -38.3 (41.5) %, p=0.001), compared to the rest of the study population who were already taking SGLT2 inhibitors or initiated them during hospitalization. Conclusion In this study we found NTproBNP, a widely used biomarker of congestion and prognosis in HF, was significantly reduced in decompensated HF patients receiving SGLT2 inhibitors, with the greatest change being observed in those being treatment-naïve prior to admission. These findings further highlight the role of this drug class even in the acute phase of the disease.Figure 1Figure 2

Evolution over time of cardiac biomarkers, electrocardiographic and echocardiographic features in a large cohort of patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis

Abstract Introduction Data on evolution of transthyretin wild-type cardiac amyloidosis (ATTRwt) during treatment with tafamidis is scarce. This hinders the quest for parameters of response and a priori treatment eligibility. Purpose To study the evolution of biomarkers, ECG, and echocardiographic features during early tafamidis treatment. Methods We prospectively collected data after 12-18 months of treatment in a single-centre database. Changes of NT-proBNP and high-sensitivity Troponin I (hs-cTnI) between baseline and follow-up evaluations (at 12 and 18 months) were tested for significance. For ECG and echocardiographic features, we considered baseline and the last available follow-up (median interval 11.1 months). Results We included 253 patients (median age 77[71-82]years; 90% males). Median (IQR) baseline NT-proBNP was 2472(1355-4749)ng/L, hs-cTnI 47(30-82)ng/L. Furosemide was administered in 58% of cases (median dose 25[25-50]mg/day). Compared to baseline, NT-proBNP was 2342(1316-4148)ng/L at 12 (p=0.886), and 2633(1393-6063)ng/L at 18 months (p=0.285), with 4% and 30% of patients showing ≥30% and ≥300ng/L increase at 12 and 18 months, respectively; hs-cTnI was 46(29-70)ng/L at 12 (p=0.947), and 44(25-68)ng/L at 18 months (p=0.866), with 35% and 7% showing a ≥20% increase at 12 and 18 months, respectively, and 21 (11.5% over 183 analyzable) with increase at 12 and reduction at 18 months. Patients on furosemide were 69% and 70% at 12 and 18 months, respectively; the dose increased to 37.5(25-75)mg/day at 18 months (p=0.009). At baseline, 117(47%) patients had history/permanent atrial fibrillation (AF). Forty-one(16%) had an implantable electronic device, 16(6%) underwent subsequent implantation. Median PR interval was 210(185-240)msec, trending toward prolongation (p=0.054). QRS duration increased (100[86-130]vs120[90-140]msec, p=0.004), together with conduction disturbances (left anterior fascicular block 30[21%]vs43[29%], p=0.036; right bundle branch block 14[10%]vs27[18%], p=0.002). AF prevalence raised from 19% to 25%. There were no significant changes in left ventricular (LV) geometry (septum thickness 18[16-20]vs18[16-20]mm, p=0.666; end-diastolic diameter 45±7vs45±8mm, p=0.434), systolic function (ejection fraction 51±10%vs49±11%, p=0.070), filling pressures (E/e’ 17[11-20]vs14.9[13-19], p=0.086) and left atrial size (mean volume 46±15vs48±13ml/m2, p=0.649). Tricuspid annular plane systolic excursion (18±4vs17±4mm) and pulmonary artery systolic pressure (40[33-45]vs36[30-45]mmHg) remained stable. Conclusions We did not observe neither improvement nor worsening of laboratory/instrumental variables within the first 12-18 months of tafamidis. There was a progression of electrical disorders. After initial progression hs-cTnI tended to improve. Extended follow-up and a matched case-control series will help identify possible later changes useful to monitor treatment response and effects of supporting heart failure treatments.

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis &amp;lt; 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.

A phase 2, randomized, double-blind, placebo-controlled study to assess the tolerability and pharmacodynamic effects of CRD-740, a PDE9 inhibitor, in participants with chronic heart failure

Abstract Background Natriuretic peptide (NP) receptor activation has a beneficial role in the treatment of heart failure (HF). The enzyme phosphodiesterase (PDE) 9 breaks down cGMP, the second messenger stimulated by natriuretic peptides. PDE9 inhibition may increase intracellular cGMP signaling and, potentially, have beneficial effects in HF. We examined the effects of the selective PDE9 inhibitor CRD-740 on the NP signaling pathway in HF. Purpose The objectives of this early phase 2 trial were to assess the tolerability of CRD-740 and its effects on plasma and urinary cGMP (markers of potential clinical effiacy) in patients with HFrEF, including those receving background treatment with sacubitril/valsartan. Methods Key inclusion criteria were patients with a history of HFrEF of &amp;gt; 6 mos, NYHA II or III, EF &amp;lt; 40% and NT-proBNP ≥600 pg/ml at screening (≥1000 pg/mL if in atrial fibrillation), on treatment with stable guideline-directed therapy for a minimum of 4 weeks. Patients were randomized 2:1 double-blind to CRD-740 (10mg twice daily for 2 weeks, then 25mg twice daily for 10 weeks) or placebo. Tolerability and safety were assessed. The primary pharmacodynamic endpoint was the between-group change from baseline in plasma cGMP at Week 4. Exploratory endpoints included urine cGMP levels, KCCQ and biomarkers. Results 60 patients were randomized to CRD-740 (n=40) or placebo (n=20). Baseline characteristics included age 67+13 yrs, 85% men, EF 28+7%, BMI 30+10, with 73% of patients taking sacubitril/valsartan, and 47% on SGLT2 inhibitors. The primary endpoint was positive, with placebo-corrected change in plasma cGMP significantly increased at all time points at week 4 in those treated with CRD-740 (see Table). cGMP levels were also increased on day 1 (Table) and week 2. A significant increase in urinary cGMP also was observed with CRD-740 vs placebo (Figure) in 6-hour collections at day 1 (p=0.012) and week 2 (p=0.014). In this small study, not powered for exploratory endpoints, directionally favorable placebo-corrected, baseline-adjusted changes also were seen in the KCCQ Clinical (+7.1 [95%CI, -1.6, +15.7], p=0.11) and Overall Summary Scores (+7.4 [-0.8, +15.5], p=0.075) for patients on CRD-740. No significant changes in NT-proBNP were observed between treatment groups. Adverse events (AEs) were observed in 62% and 50% of CRD-740 and placebo-treated patients, with discontinuation in 5% and 10% respectively, with no between-group difference in change in BP. There were no hypotension AEs, and no treatment-related serious adverse events. Conclusions In this early phase 2 trial, PDE9 inhibition with CRD-740 was well-tolerated and resulted in substantial elevations of plasma and urinary cGMP on top of standard care, including sacubitril/valsartan. These results support the potential of PDE9 inhibition to further activate the beneficial effects of the NP receptor-cGMP pathway incrementally to that achieved by existing HF treatments.Changes in Plasma cGMP over Time (ng/mL)Changes in Urinary cGMP over Time

Safety and efficacy of initiation SGLT in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease on top of standard therapy with ARNI or ACE-i

Abstract Quadruple therapy remains underused in cases of heart failure with a reduced ejection fraction (HFrEF). Among eligible patients most of them take ACE-i/ARB and B-blockers, less MRAs and ARNI. There are many questions of adding new foundational drugs, especially in the case of coexisting of HFrEF and chronic kidney disease (CKD). The aim was to compare the safety and effectiveness of initiation SGLT in patients (P) with HFrEF and CKD on standard therapy with ARNI or ACE-I. Methods we identified 54 symptomatic P with HFrEF (EF≤40%) and CKD 3 (eGFR between 30 and 60 ml/min) on standard therapy (ACE-I or ARNI, B-blockers, MRAs). All P were divided into 2 groups: group 1- 26 P on ARNI, B-blockers, MRAs; group 2- 28 P on ACE-I, B-blockers, MRAs. All P started on dapagliflozin (D) with a dose of 10 mg daily. The potassium (K), creatinine levels, eGFR, clinic BP were estimated at baseline and at weeks 1, 2, 4, 6, 8, 12. At baseline and at weeks 4, 12 NT-proBNP, urine albumin-to-creatinine ratio (UCAR) were estimated and P underwent 24-hour BP measurements. Results At week 1 after initiation of D a mean eGFR deсreased not significant in both group. At week 2 in group 1 mean eGFR decreased by 1,9±1.1 ml/min/1.73m2, P&amp;lt;.05 and group 2-2,5±1.9 ml/min/1.73m2, P&amp;lt;.05. At week 4 in both groups mean eGFR deсreased significantly, but in group 2 the decline of eGFR was more pronounced (-2,4±2.6 ml/min/1.73m2 vs.-3,3±2.5 ml/min/1.73m2, P=.04), with not significant decreasing to 6, 8, 12 weeks. At week 1mean K changed not significantly after start of therapy in both groups. At week 4 in group 1mean K deсreased significantly from 4.97±0.6 to 4.63±0.57 mEq/l (P&amp;lt;.05), in group 2 K deсreased not significant. At week 4 in group 1 was a greater reduction NT-proBNP than in group 2 (-234±42 vs. -143±32 ng/L, P&amp;lt;.05). At week 12 in both groups a significant decrease NT-proBNP were observed, but in group 1 more pronounced (-865±89 ng/L and -573±78 ng/L, (P&amp;lt;.01; P&amp;lt;.05 respectively). UCAR was also reduced significantly in both groups, but in group 1 more pronounced (P&amp;lt;.01; P&amp;lt;.05 respectively). In group 1, there were more cases of symptomatic hypotension (10 vs. 8, P&amp;lt;.05) and greater decrease mean BP than in group 2 (P&amp;lt;.05), but it didn’t result in a withdrew. In return, maen doses diuretics were carefully decreased in both groups. At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.328, P&amp;lt;.05). By linear regression analysis the eGFR was associated with NT-proBNP change (P&amp;lt;.05). Conclusion In patients with HFrEF and CKD, adding SGLT to standard therapy with ARNI, B-blockers, MRAs were paralleled by marked improvements in the neurohumoral profile by significantly reduced NT-proBNP compared with ACE-I, B-blockers, MRAs. SGLT initiation caused an early drop in eGFR, but in group ARNI the decline of eGFR was less pronounced with greater reduction in the albuminuria and was accompanied by decreased potassium level.

Do I sound sick? Self-perceived and objectively measured voice impairment in acutely decompensated heart failure: fist insights from the AHF-Voice study

Abstract Introduction Acute heart failure (AHF) is a common reason for recurrent hospitalization. Daily smartphone-based recording of vocal biomarkers appears promising for the early detection of impeding AHF. However, the value of patient-reported outcome measures (PROMs), i.e. self-perceived voice alterations during decompensation, is unknown. Methods AHF-Voice is an ongoing monocentric prospective cohort study focusing on voice alterations in patients hospitalized for AHF. Exclusion criteria: listed for heart transplantation, high output HF, cardiogenic shock, history of vocal fold disease or surgery, or life-expectancy &amp;lt;6 months. During hospitalization, medical history &amp; echocardiogram were taken and routine blood sampling was done. Daily voice recordings including sustained vowels and standardized reading were collected using a specially designed smartphone app under supervision. At admission and discharge, the self-perceived level of voice alteration was assessed by the Voice–Handicap Index-12 (VHI-12, 0-48 points) questionnaire and a global voice scale (Likert scale, 0-3 points). For both scales, higher values indicate a more severe voice impairment. Hypervolemia was quantified by body composition analysis. Preprocessing and feature extraction of voice recordings were performed using Praat software. The association of self-perceived voice impairment with surrogates of congestion and vocal biomarkers was assessed by bivariate correlation and linear regression. Results Between Apr 2023 and Feb 2024, 72 hospitalized patients with AHF were included. Four patients withdrew consent, 5 patients were excluded due to limited voice recording quality. Hence, 63 patients were considered for analysis: mean age 75±10 years, 67% men, 91% were in NYHA class III/IV, 49% de novo HF, mean LVEF was 45±16%, and median value of Charlson comorbidity score was 2 [1, 3]. Both measures of self-perceived voice impairment improved between admission and discharge (Table 1A and Figure). Concomitantly, body weight, hypervolemia, NT-proBNP, and vocal biomarkers (total reading time and shimmer) decreased. Bivariate correlation showed that both self-perceived scales of voice impairment were closely correlated, as expected (Spearman’s rho 0.36). Linear regression identified surrogates of congestion and objective voice impairments as predictors for change in both PROMs (Table 1B). However, the explained variance was low, e.g. for change in volume status and NT-proBNP 14% and 1% (VHI-12), and 4% and 7% (Global voice scale), respectively. Conclusion This preliminary analysis in patients with AHF showed that self-perceived voice impairment was sensitive to change during recompensation. Objectively generated voice measures and congestion only partially explained the observed improvement of these PROMs. This might indicate that the self-perceived voice impairment constitutes a complimentary domain of patient well-being and indicator for congestion that should be explored further.

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: mitral fibrin study

Abstract Background/Introduction The management of heart failure (HF), particularly in the context of reduced ejection fraction, is further complicated by an increased risk of thromboembolic events. Structural alterations of both left ventricle and mitral valve contribute to mitral regurgitation (MR). However, the body of evidence provides inconclusive insights into the relationship between MR and thromboembolic risk. Purpose This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on thrombin generation, clot permeation and clot lysis time in HF patients with severe MR eligible for mitral TEER. Methods A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points. Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed. Comprehensive evaluations also covered echocardiographic, laboratory, and clinical parameters. Results TEER induced changes in fibrinogen levels (p=0.009, visit 3 vs. visit 2) and improved fibrin clot properties over a 50-day follow-up (Ks, p=0.005, visit 3 vs. visit 2). No significant differences were observed among time points in analyzed blood clot parameters. Linear regression, incorporating thrombin generation variables, Ks, and CLT for delta NT-proBNP, highlighted CLT as the sole predictor of NT-proBNP change between visit 2 and visit 1 (p=0.03; R2=0.18). Conclusions MR reduction through TEER led to transient alterations in fibrinogen concentration and improved fibrin clot characteristics. Additionally, baseline CLT emerged as a significant predictor of early NT-proBNP reduction, emphasizing its role as a key indicator of the hemodynamic response to TEER.

Angiotensin receptor-neprilysin inhibition and improved ventricular-arterial coupling in heart failure with reduced ejection fraction.

Sacubitril/valsartan improves outcome in chronic heart failure (HF) with reduced ejection fraction (EF). The underlying mechanisms on left ventricular (LV) myocardial function are incompletely understood. In this study, 117 patients with symptomatic HF and LV-EF ≤ 40% were enrolled prospectively. Non-invasive pressure-volume analysis was calculated from transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements. Primary outcome parameters were LV end-systolic elastance (Ees; a measure of LV contractility), effective arterial elastance (Ea; a measure of afterload), and the ventricular-arterial coupling ratio (Ea/Ees). Mean age was 65±13 years, 30% were female, and 54.7% had ischemic heart disease. During six months of follow-up, eight patients died, three withdrew their consent, and four were lost to follow-up. 102 patients were included in pressure-volume analyses. After six months of sacubitril/valsartan treatment, Ees increased (0.66mmHg/ml [IQR 0.45-0.94] vs. 0.78mmHg/ml [IQR 0.57-1.10], p=0.001), Ea decreased (1.76mmHg/ml [IQR 1.48-2.13] vs. 1.62mmHg/ml [IQR 1.36-1.96], p=0.014), and the Ea/Ees ratio improved (2.52 [IQR 1.88-4.05] vs. 1.93 [IQR 1.50-2.63], p<0.001). LV end-diastolic pressure and LV volumes were reduced, and LVEF increased from 33% to 43% (both p<0.001). Clinical improvement occurred in NYHA functional class, NT-proBNP level, and 6-minute walking distance. Change in LVEF correlated with change in Ees (r=0.33, p=0.0008), while change in NT-proBNP was associated with change in LVEDP (r=0.42, p<0.0001). In conclusion, sacubitril/valsartan is associated with improved ventricular-arterial coupling by enhancing LV contractility and reducing afterload. Beyond LV reverse remodeling, optimized ventricular-arterial interaction may contribute to the favorable outcome of sacubitril/valsartan treatment in HF with reduced EF.

Impact of transcatheter edge to edge repair in functional mitral regurgitation and cardiac resynchronization-therapy nonresponders.

Despite optimal medical therapy and cardiac resynchronization therapy (CRT), significant functional mitral regurgitation (MR) persisted in 30% of the patients and labeled as CRT nonresponders. We sought to study the impact of transcatheter edge-to-edge repair (TEER) in patients with symptomatic grade III and IV functional MR despite CRT. A retrospective analysis was conducted of all patients who had prior CRT for at least 6 months and underwent TEER for significant residual functional MR (grade ≥3) and symptomatic heart failure (HF) at our institution. The primary outcomes were the change in New York Heart Association classification (NYHA), MR grade, echo parameters, and NT-ProBNP from baseline to 1-year post-procedure. A total of 28 patients were identified, mean age of 73 ± 6.7 years and 89% males. Procedure success was achieved in all patients. At 1-year follow-up, patients had lower MR grade (median 2, IQR 1 [1,2] vs. 4, IQR 1 [3,4]; p < 0.001), NYHA class (median 2, IQR 1 [2,3] vs. 3, IQR 1 [3,4]; p < 0.001), and NT-ProBNP (7658 ± 11322 vs. 3760 ± 4431; p = 0.035) compared to before the TEER procedure. The left ventricular end-diastolic volume (255 ± 59vs. 244 ± 66 mm; p = 0.016) and the right ventricular systolic pressure (52 ± 14 mmHg vs. 37 ± 13 mmHg, <0.001) decreased. Patients who remain symptomatic after CRT with severe functional MR had improved functional status and MR grade at 1-year following TEER. There was a signal toward reverse remodeling.

Changes in blood biomarkers correlate with changes in cardiac size and function in patients with tetralogy of Fallot

IntroductionPatients after surgical correction of Tetralogy of Fallot (ToF) often show adverse cardiac remodeling. To better understand the underlying biological processes, we studied the relation between changes in blood biomarkers and changes in biventricular size and function as assessed by cardiac magnetic resonance imaging (CMR). MethodsThis study included 50 ToF patients, who underwent blood biomarker and CMR analysis at least twice between 2002 and 2018.34 (68 %) of these patients were male. Patients had an average age of 16.1 at first visit. Biomarkers were chosen based on earlier research by our group and included: NT-proBNP, ST2, GDF-15, DLK-1, IGFBP-1/7, and FABP-4. Pearson correlations coefficients (rpearson) were determined to quantify the relationship between changes in biomarkers and CMR measurements. ResultsFor changes in parameters of right ventricular (RV) size significant correlations were observed with changes in NT-proBNP, ST-2, GDF-15, IGFBP7 and FABP-4 (rpearson between 0.28 and 0.51). Correlations with NT-proBNP were driven by changes in RV size induced by pulmonary valve replacement (n = 9). For LV serial size changes, significant correlations were noted with changes in NT-pro-BNP, ST-2, GDF-15 and FABP-4 (rpearson between 0.32 and 0.52). ConclusionIn clinically stable ToF patients changes in right and left ventricular size and function correlated with alterations in blood biomarkers of inflammation and immune response to stress.

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: Mitral Fibrin Study.

Intricate management of heart failure (HF), especially in the context of reduced ejection fraction, is further complicated by an elevated risk of thromboembolic events. Studies published so far offer inconclusive insight into the interplay between mitral regurgitation (MR) and the coagulation system. This study aimed to investigate the impact of transcatheter edge‑to‑edge repair (TEER) on specific coagulation parameters in HF patients. A cohort of 31 HF patients with severe MR treated with TEER underwent a systematic evaluation at 3 visits (V1, V2, and V3). Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability, and clot lysis time (CLT) were assessed (n = 27 at V2; n = 25 at V3). TEER induced changes in fibrinogen levels (P = 0.01; V3 vs V2) and improved fibrin clot properties over 50‑day follow‑up (P = 0.01; V3 vs V2). No significant differences were observed between time points in the analyzed blood clot parameters. Correlation analysis showed that baseline CLT was associated with ΔN‑terminal pro-B‑type natriuretic peptide (NT‑proBNP) level (P = 0.049; r = 0.4). Multivariable analysis identified baseline CLT as an independent predictor of early post‑TEER NT‑proBNP change (R2 = 0.55; P = 0.02). We found decreased level of fibrinogen and increased permeation coefficient over a median 50 (interquartile range, 32.5-75.5)-day post‑TEER follow‑up, as compared with early postprocedural assessments. Other blood coagulation parameters remained unchanged from baseline at both follow‑up time points after TEER. Finally, CLT was an independent predictor of early NT‑proBNP increase, emphasizing its role as an indicator of hemodynamic response to TEER.

Association of Sacubitril/Valsartan vs Valsartan With Blood Pressure Changes and Symptomatic Hypotension: the PARAGLIDE-HF Trial

In PARAGLIDE-HF, among patients with ejection fraction (EF) >40%, stabilized after worsening heart failure (WHF), sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared to valsartan alone, despite more symptomatic hypotension (SH). Concern over SH may be limiting use of sacubitril/valsartan in appropriate patients. We characterized patients by the occurrence of SH (investigator-reported) after randomization to either sacubitril/valsartan or valsartan. A key trial inclusion criterion was systolic blood pressure (SBP) ≥100 mmHg for the preceding 6 hours and no SH. We also compared outcomes based on baseline SBP stratified by the median blood pressure. The primary endpoint was time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: a) cardiovascular death, b) HF hospitalizations, c) urgent HF visits, and d) change in NT-proBNP. Among 466 randomized patients, 92 (19.7%) experienced SH (sacubitril/valsartan, N=56 [24.0%]; valsartan, N=36 [15.5%], p=0.020). The median time to the first SH event was similar between treatment arms (18 days vs. 15 days, respectively, p=0.42) as was the proportion of first SH events classified as "serious" by investigators. Patients who experienced SH with sacubitril/valsartan were more likely to be White (OR 1.87 [95%CI: 0.31, 11.15]), to have a lower baseline SBP (per 10mmHg increase OR 0.68 [95%CI: 0.55, 0.85]), or to have a left ventricular ejection fraction (LVEF) of >60% (OR 2.21 [95%CI: 1.05, 4.65]). Time-averaged change in NT-proBNP did not differ between patients with baseline SBP ≥128 mmHg vs. SBP<128mmHg (interaction p=0.43). The composite hierarchical outcome for sacubitril/valsartan in patients with baseline SBP≥128mmHg had a win ratio of 1.34 ([95%CI: 0.91, 1.99], p=0.096) vs SBP<128mmHg with a win ratio of 1.09 ([95%CI: 0.73, 1.66], p=0.62; interaction p value=0.42). Among patients with LVEF>40% stabilized after WHF, incident SH was more common with sacubitril/valsartan compared with valsartan. SH was associated with lower baseline SBP, White race, and higher LVEF. Treatment benefits with sacubitril/valsartan may be more pronounced in patients with higher baseline SBP and lower LVEF (≤ 60%). (Funded by Novartis Pharmaceutical Corporation; ClinicalTrials.gov number, NCT03988634.) ABBREVIATIONS: : HFpEF, heart failure with preserved ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFrEF, heart failure with reduced ejection fraction; LVEF, left ventricular ejection fraction; NT-proBNP, amino terminal-pro b-type natriuretic peptide; SBP, systolic blood pressure; WHF, worsening heart failure.

(841) - Association of Longitudinal Changes in NT-proBNP Following HeartMate 3 Implant with Subsequent Long-Term Clinical Outcomes

(841) - Association of Longitudinal Changes in NT-proBNP Following HeartMate 3 Implant with Subsequent Long-Term Clinical Outcomes

Impact of HIF prolyl hydroxylase inhibitors in heart failure patients with renal anemia

ObjectiveHypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of anti-anemia agents. We retrospectively evaluated the safety and efficacy of HIF-PH inhibitors in patients with heart failure (HF) complicated by anemia associated with chronic kidney disase. HIF-PH inhibitor treatment was initiated in 32 patients with chronic HF complicated by renal anemia and were followed up for 3 months.ResultsHematocrit and hemoglobin levels markedly improved 3 months after HIF-PH inhibitor treatment. However, levels of NT-proBNP, which is an indicator of HF, did not decrease considerably. Based on the rate of change in NT-proBNP, we divided the patients into “responder” and “non-responder” groups. The results showed that considerably more patients had a ferritin level of less than 100 ng/mL in the non-responder group at baseline. There were substantially more patients with TSAT of less than 20% in the non-responder group at 1 month after HIF-PH inhibitor treatment. The cut-off values to maximize the predictive power of ferritin level at baseline and TSAT value at 1 month after treatment were 41.8 ng/ml and 20.75. HIF-PH inhibitor treatment can be expected to be effective for improving both anemia and HF if ferritin≥41.8 ng/ml at baseline or TSAT≥20.75 at 1 month after treatment.

Simultaneous initiation of quadruple therapy for heart failure with reduced ejection fraction: initial experience in Afro Caribbean Jamaican population

Background: Among Afro Caribbean Jamaican patients with heart failure with reduced ejection fraction (HFrEF), improvements in cardiac function associated with simultaneous initiation of quadruple therapy, have not been previously reported and we aimed to assess this special population. Methods: Combined quadruple therapy (angiotensin-receptor neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and Sodium-glucose cotransporter-2 inhibitors) was simultaneously initiated in 120 Afro Jamaican patients with HFrEF from the Heart Institute of the Caribbean. Patient data was consecutively recorded in our electronic medical records. Changes in Ejection fraction (EF) and N-terminal pro b-type natriuretic peptide (NT-ProBNP) levels, were evaluated after 90 days and statistically analysed during this two-year study. Results: Patient mean age was 63 ± 12.7 years old, 68% male, with mean Body Mass index (BMI) 32.2±6.7 Kg/m2. Hypertension was observed in 62.5 %, T2Diabetes Mellitus in 31.7%, and history of old myocardial infarction in 15.7 %. Atrial fibrillation was present in 7.8% and left bundle branch block in 16.5 %. Other cardiomyopathies (idiopathic, peripartum and non-compaction) were noted in 16.6 %. After the quadruple therapy for a median follow-up period of 90 days, significant improvements of cardiac function were achieved. The mean NT pro-BNP level was significantly decreased from a Baseline of 3111.21 pg/mL ± 4535 to 1806.6 ± 2265.3 pg/ml. A mean change in NT Pro BNP of 1305 pg/mL ± 5069 (p &lt; 0.001). The mean left ventricle ejection fraction (LVEF) improved from a baseline of 33.4 % ± 7.8 to 44.4 % ± 10.9. A mean change in LVEF of 11.3% ± 9.1 (p &lt;0.001). Notably, an improvement of &gt;10% in the LVEF was observed in 41.5% of the total population. In a separate analysis, the subgroup with T2 Diabetes mellitus showed more pronounced (mean change in EF 9.1% ± 11.0) improvement in LVEF than the non-diabetic (mean change in EF 7.7% ± 11.7) but no significant differences in the change of the NT pro-BNP levels were noted between both subgroups. The most frequent therapy adverse effect was hypotension (13.63%) followed by cough (6.81%) and kidney dysfunction (2.27%) but none of the patients presented Angioedema. Conclusion: Among Afro Caribbean Jamaican patients with heart failure and reduced ejection fraction, simultaneous initiation of the quadruple therapy was demonstrated to be feasible, well tolerated and associated with significant functional improvement.

Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.

Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

Feasibility and safety of left bundle branch area pacing in cardiac amyloidosis. A single center experience.

Conventional right ventricle (RV) pacemaker stimulation has been associated with worse clinical outcomes in patients with cardiac amyloidosis (CA). Left bundle branch area pacing (LABPP) has been suggested as a promising alternative. We sought to assess the safety, feasibility, and outcomes of LABPP in patients with CA. We retrospectively analyzed echocardiography and pacing parameters and clinical outcomes in 23 consecutive patients with CA and LBBAP implanted from June 2020 to October 2022. LBBAP was successfully performed in 22 over 23 patients (19 male, 78.6±11.7 years, 20 ATTR, mean LVEF 45.5±16.2%). After the procedure, 9 patients showed Qr pattern and 11 a qR pattern in V1 on ECG. Average procedure time was 67±28min. After 7.7±5.2 months follow-up, no procedure-related complications had occurred. Although, a significant reduction in QRS width (p=.001) was achieved, we did not observe significant changes in LVEF and Nt ProBNP at 6 months of follow-up. Pacing parameters were stable during follow-up: LBB capture threshold and R wave amplitude were 1.0± 0.5V and 10.6±6.0 mV versus 0.8± 0.1V, p=.21 and 10.6±5.1mV (p=.985) at follow up. LBBAP is safe and feasible pacing technique for patients with CA. LBBAP is associated with significant narrowing of QRSd without worsening in LVEF and Nt-proBNP.

Repetitive LevosimenDan infusions fOR patients with advanced chronic heart failure in the vulnerable post-discharge period: the multinational randomized LeoDOR trial

Abstract Background Studies of the repetitive use of intravenous levosimendan suggested a beneficial effect in patients with advanced heart failure (HF). It was the aim of the LeoDOR trial to test the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute HF. Methods In this multicenter, double-blind, three-armed trial with an enrolment period from 3-2018 to 6-2021, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or placebo for a period of 12 weeks. Levosimendan was administered according to center preference either as 6-hour infusion at a rate of 0.2 mcg/kg/min every 2 weeks, or as 24-hour infusion at a rate of 0.1 mcg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank endpoint consisting of three hierarchical groups: Tier 1 = time to death or urgent heart transplantation or implantation of a ventricular assist device; Tier 2 = time to non-fatal HF requiring i.v. vasoactive therapy; Tier 3 = time-averaged proportional change in NTproBNP from baseline to week 14. Results Due to a forced interim interruption of the study as a result of the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat (mITT) analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm). Patient characteristics were well balanced between treatment and placebo arms (mean age 69.3±9.7 vs 67.9±10.1, proportion of women 22.6% vs 21.2%, HF-hospitalizations in previous 12 months 1.9±1.4 vs. 1.7±1.1, NTproBNP at baseline 4740 ng/L (IQR 2235 – 9016) vs 5380 ng/L (IQR 2287 – 8204). There were no marked differences regarding HF medication and implanted devices. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint (mean rank score 71.8 for the levosimendan group vs 75.1 for the placebo group; p = 0.65). However, there was a strong signal towards a higher incidence of the individual clinical components of the primary endpoint (tier 1 plus tier 2) in the levosimendan group vs the placebo group both after 14 weeks (HR 2.94, 95%CI 1.13–7.70; p = 0.028) and 26 weeks (HR 1.65 95%CI 0.87 – 3.12; p = 0.123). The number of investigator-reported adverse events during and immediately after drug application was 12.4% in the levosimendan group vs 11.8% in the placebo group (p = 0.905). Conclusion Our findings do not support the use of intermittent levosimendan to improve post-hospitalization clinical stability in patients who were recently hospitalized with HF and reduced LVEF. Further studies are warranted to find the correct use of levosimendan in advanced heart failure patients.