scholarly journals The myosin activator: is another step forward in heart failure therapy?

2021 ◽  
Vol 23 (Supplement_E) ◽  
pp. E151-E155
Author(s):  
Raffaele Abete ◽  
Attilio Iacovoni ◽  
Michele Senni
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Contractility ◽  
Composite Endpoint ◽  
Standard Of Care ◽  
First Episode ◽  
Cardiac Myosin ◽  
Heart Failure Therapy ◽  
New Class ◽  
Current Guidelines

Abstract Selective cardiac myosin activators constitute a new class of drugs capable of increasing cardiac contractility independently of intracellular calcium concentrations. In the GALACTIC-HF study, the first of this class of molecules, omecamtiv mercabil, was compared with the standard of care according to current guidelines, showing a significant reduction in the composite endpoint of first episode of heart failure or mortality due to cardiovascular causes in patients exposed to treatment compared with placebo. In particular, the effect was more pronounced for decreasing ejection fraction values, suggesting a potential further benefit of selective cardiac myosin activators in this category of patients.

Prognostic role of sonographic decongestion in patients with acute heart failure with reduced and preserved ejection fraction: a multicentre study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N.R Pugliese ◽  
M Mazzola ◽  
G Bandini ◽  
G Barbieri ◽  
S Spinelli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Ejection Fraction ◽  
Acute Heart Failure ◽  
Vena Cava ◽  
Composite Endpoint ◽  
Clinical Findings ◽  
Preserved Ejection Fraction ◽  
Net Reclassification Improvement ◽  
B Lines

Abstract Aims Our aim was to assess the dynamic changes of pulmonary congestion (PC) through variations of sonographic B-lines, in addition to conventional clinical, biohumoral and echocardiographic findings, to improve prognostic stratification of patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods In this multicenter, prospective, observational study, lung ultrasound was performed in all patients at admission and before discharge by trained investigators, blinded to clinical findings and outcomes. Results We enrolled 208 consecutive patients admitted for acute heart failure (125 HFrEF, 83 HFpEF, mean age 75.9±11.7 years, 36% females, mean ejection fraction 38%). After 180-day follow-up, 38 composite endpoint events occurred (cardiovascular deaths or HF re-hospitalisations). In a multivariate model, B-lines at discharge had independent prognostic value in the overall population together with NT-proBNP, moderate-to-severe mitral regurgitation (MR) and inferior vena cava diameter at admission. When dividing the population in HFrEF and HFpEF, B-lines at discharge was the only independent parameter to predict events in all subgroups. At ROC analysis, a cut-off of B-lines>15 at discharge displayed the highest accuracy in predicting adverse events (AUC=0.80, p<0.0001). The identification of patients unable to halve B-lines during hospitalization (ΔB-lines%), in addition to B-lines >15 at discharge, improved event classification (integrated discrimination improvement=4%, p=0.01; continuous net reclassification improvement=22.8%, p=0.04). Conclusions The presence of residual subclinical sonographic PC at discharge predicts adverse events in the whole spectrum of acute HF patients, independently of conventional biohumoral and echocardiographic parameters. The dynamic evaluation of pulmonary decongestion during hospital stay can further improve patient risk stratification. Funding Acknowledgement Type of funding source: None

4181Prognosis of patients with mid-range left ventricular ejection fraction treated with PCI: insight from the global leaders study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Chichareon ◽  
R Modolo ◽  
N Kogame ◽  
M Tomaniak ◽  
E Teiger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Stent Thrombosis ◽  
Composite Endpoint ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality

Abstract Background Heart failure with mid-range ejection fraction (left ventricular ejection fraction between 40 to 49%) was introduced in the 2016 European Society of Cardiology guidelines for heart failure. The prognosis of the mid-range of left ventricular ejection fraction (LVEF) was less well assessed in patients treated with percutaneous coronary intervention (PCI). Purpose We aimed to assess the 2-year outcomes of patients with mid-range ejection fraction (LVEF between 40 to 49%) after PCI compared with reduced LVEF (<40%) and preserved LVEF (≥50) in the GLOBAL LEADERS study. Methods The GLOBAL LEADERS study was a multicenter, randomized trial comparing the efficacy and safety of two antiplatelet strategies in all-comers patients undergoing PCI with biolimus-A9 eluting stent. Patients with available information of LVEF were eligible in the present analysis. Patients were classified according to their LVEF into three groups; preserved (LVEF ≥50), mid-range (LVEF 40–49%) and reduced (LVEF <40%) left ventricular ejection fraction. Clinical outcomes at 2 years after PCI were compared among three groups in the multivariable Cox regression analysis. The primary outcome of present study was all-cause mortality at 2 years after PCI. The secondary outcomes were patient-oriented composite endpoint (POCE). Individual components of the composite endpoint, definite or probable stent thrombosis and bleeding academic research consortium (BARC) type 3 or 5 were also reported. Results Out of 15968 patients included in the GLOBAL LEADERS study, information of LVEF was available in 15008 patients (93.99%); 12,128 patients (80.81%) were in the group of preserved LVEF, 1,737 patients (11.57%) were in the mid-range LVEF group and 1,143 patients (7.62%) were in the reduced LVEF group. The risk of all-cause mortality and POCE at 2 years were significantly different among the three groups. In an adjusted model, compared with the group of preserved LVEF, the hazard ratio for the all-cause mortality at 2 years rose from 1.89 (95% CI, 1.46–2.45) to 3.72 (95% CI, 2.95–4.70) in the group of mid-range and reduced LVEF respectively. Similar rises were observed for the POCE at 2 years from 1.27 (95% CI, 1.11–1.44) in the group of mid-range LVEF to 1.63 (95% CI, 1.42–1.87) in the group of reduced LVEF. The risk of stroke, myocardial infarction, and definite or probable stent thrombosis in patients with mid-range LVEF was not different from patients with reduced LVEF (see figure). A similar risk of revascularization was observed among the three groups. Outcomes among three LVEF categories Conclusion Patients with mid-range LVEF undergoing PCI had a different prognosis from patients with reduced LVEF and preserved LVEF in term of survival and composite ischemic endpoints at 2 years.

scholarly journals Cornell product is an ECG marker of heart failure with preserved ejection fraction

Heart Asia ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. e011108 ◽  
Author(s):  
Eugene SJ Tan ◽  
Siew Pang Chan ◽  
Chang Fen Xu ◽  
Jonathan Yap ◽  
Arthur Mark Richards ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Asian Population ◽  
Composite Endpoint ◽  
Left Ventricular ◽  
Healthy Controls ◽  
Preserved Ejection Fraction ◽  
S Wave ◽  
All Cause Mortality ◽  
Cornell Product

ObjectiveECG markers of heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We hypothesised that the Cornell product (CP) is a risk marker of HFpEF and has prognostic utility in HFpEF.MethodsCP =[(amplitude of R wave in aVL+depth of S wave in V3)×QRS] was measured on baseline 12-lead ECG in a prospective Asian population-based study of 606 healthy controls (aged 55±10 years, 45% men), 221 hypertensive controls (62±9 years, 58% men) and 242 HFpEF (68±12 years, 49% men); all with EF ≥50% and followed for 2 years for all-cause mortality and HF hospitalisations.ResultsCP increased across groups from healthy controls to hypertensive controls to HFpEF, and distinguished between HFpEF and hypertension with an optimal cut-off of ≥1800 mm*ms (sensitivity 40%, specificity 85%). Age, male sex, systolic blood pressure (SBP) and heart rate were independent predictors of CP ≥1800 mm*ms, and CP was associated with echocardiographic E/e′ (r=0.27, p<0.01) and left ventricular mass index (r=0.46, p<0.01). Adjusting for clinical and echocardiographic variables and log N-terminal pro B-type natriuretic peptide (NT-proBNP), CP ≥1800 mm*ms was significantly associated with HFpEF (adjusted OR 2.7, 95% CI 1.0 to 7.0). At 2-year follow-up, there were 29 deaths and 61 HF hospitalisations, all within the HFpEF group. Even after adjusting for log NT-proBNP, clinical and echocardiographic variables, CP ≥1800 mm*ms remained strongly associated with a higher composite endpoint of all-cause mortality and HF hospitalisations (adjusted HR 2.1, 95% CI 1.2 to 3.5).ConclusionThe Cornell product is an easily applicable ECG marker of HFpEF and predicts poor prognosis by reflecting the severity of diastolic dysfunction and LV hypertrophy.

P6288Autoantibodies in heart failure associate with disease severity and differentially expressed genes in apoptotic, fibrotic, and hypoxia pathways in cardiomyocytes

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Myers ◽  
C Sandel ◽  
K Alvarez ◽  
L Garman ◽  
K White ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Hypertrophy ◽  
Dilated Cardiomyopathy ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Differentially Expressed ◽  
Heart Cell ◽  
Cardiac Myosin

Abstract Background Previous studies suggest that autoantibodies against cardiac myosin lead to dilated cardiomyopathy (DCM). Anti-cardiac myosin antibodies cross-react with the beta adrenergic receptor (βAR) and signal cAMP-dependent protein kinase A (PKA) in cardiomyocytes leading to apoptosis, fibrosis, dilated cardiomyopathy and arrhythmias. Purpose To determine if cross-reactive anti-cardiac myosin/anti-βAR autoantibodies which signal cardiomyocytes through PKA might play a role to establish DCM by promoting remodeling, apoptosis, and fibrosis. Methods Forty-one adults with DCM were enrolled <6 months from symptom onset and followed for 12 months. Serum and myocarditis/DCM-derived human mAb were analyzed by ELISA for autoantibodies, and a PKA assay measured anti-HCM/βAR antibody-mediated signaling of cardiomyocytes (ATCC primary heart cell line H9c2). The top 50 genes differentially expressed in the cardiomyocytes treated with sera or human mAb were identified and compared to genes differentially expressed in blood of DCM patients to identify shared disease-specific genes. Results Anti-HCM autoantibodies including autoantibody responses against 32 overlapping synthetic peptides of the S2 fragment of HCM were significantly elevated in patients whose ejection fraction did not improve over 1-year compared to those with improved ejection fraction. The human mAb confirmed our results with HCM, βAR, specific HCM peptides, and PKA signaling. RNA sequencing revealed differentially expressed genes in serum/mAb-treated cardiomyocytes compared to genes identified after RNA sequencing of peripheral blood of patients (n=10) with DCM for >1 year from onset. A primary heart cell line (H9c2-ATCC) treated with myocarditis/DCM patient sera or human mAb revealed differentially expressed genes associated with cardiac hypertrophy and heart failure, and included inflammasome component NLRP3 and complement factor H. Ingenuity Pathway Analyses revealed 27, 7, and 1 differentially expressed genes related to apoptosis, fibrosis, and hypoxia, respectively. Gene expression of CASZ1, a transcription factor important in protection against DCM, was strongly correlated with PKA signaling (r=0.89). The KDM6B gene for lysine demethylase associated with hypoxia and apoptosis pathways and was shared between cardiomyocyte and peripheral blood analysis of DCM patients. Overall, 5 genes were shared in heart failure vs in vitro Ab-treated cardiomyocyte RNA sequencing analysis: CYP4F3, KDM6B, MBOAT7, SMAP2, and DDIT4, which affects phosphorylation of mTOR to promote autophagy and cell death, cardiac hypertrophy and dysfunction. Conclusions Significantly higher responses to cardiac myosin in patients with DCM were related to lack of left ventricular function improvement and to differential expression of genes promoting apoptosis, fibrosis and disease severity. These studies identify autoantibody-directed gene signaling as a potential novel therapeutic target in DCM. Acknowledgement/Funding National Heart, Lung, and Blood Institute, Bethesda, MD, USA

scholarly journals 164 Effect of cardiac contractility modulation therapy on myocardial work in patients with heart failure with reduced ejection fraction

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Daniele Masarone ◽  
Stefano De Vivo ◽  
Vittoria Errigo ◽  
Antonio D’ Onofrio ◽  
Giuliano D’Alterio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Contractility Modulation ◽  
Reduced Ejection Fraction ◽  
Constructive Work ◽  
Global Work ◽  
The Impact

Abstract Aims Cardiac contractility modulation therapy (CCMT) has been shown to reduce hospitalizations and to improve quality of life in heart failure patients with reduced ejection fraction (HFrEF) who remain symptomatic despite disease-modifying therapies. Strain imaging derived myocardial work (MW) is an emerging tool for evaluating left ventricular mechanics by incorporating systolic deformation and afterload burden in the analysis. To evaluate prospectively the impact of CCMT in HFrEF patients on MW derived parameters in relation to standard echocardiographic indices. Methods and results We recruited 12 HFrEF patients with indications to CCMT according to current clinical practice. A comprehensive echo-Doppler evaluation, including speckle tracking derived assessment of global longitudinal strain (GLS), was performed before and after three months from the CCM device implantation. Parameters of MW such as global work index (GWI), global constructive work (GCW) global wasted work (GWW), and global work efficiency (GWE) were calculated according to standardized procedures. Median values (interquartile range) were compared for all those parameters from baseline and 3-month follow-up with Wilcoxon Rank Sum test for continuous variables. At three months from CCM implant an improvement of LVEF [from 32% (27–34) to 36% (29–39), P &lt; 0.05], GLS [from 7.4% (6.2–11.2) to 9.9% (7.5–9.4), P &lt; 0.05], GWI [from 461 mmHg (372–613) to 589 mmHg (413–696), P &lt; 0.05], GCW [from 800 mmHg (620–930) to 970 mmHg (644–1009), P = 0.236], and GWE [from 73% (65–78) to 85% (78–87), P &lt; 0.05] was observed, with a consistent reduction of GWW [from 161 mmHg (148–227) to 125 mmHg (101–188), P &lt; 0.05]. We also found a positive correlation between the magnitude of LVEF improvement and the baseline values of GCW (r = 0.727, P = 0.011). Conclusions At 3 months, CCMT significantly improves standard and advanced left ventricular systolic function indices. This improvement is due to the increase of constructive work and a reduction of wasted work. In addition, the increase of left ventricular ejection fraction can be predicted by the global constructive work levels at baseline.

Sign in / Sign up

Export Citation Format

Share Document