P5440Systolic/diastolic effects of chronic treatment with omecamtiv mecarbil in minipigs with post-myocardial infarction Heart Failure with reduced Ejection Fraction (HFrEF)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Caillaud ◽  
X Baudot ◽  
L Gouraud ◽  
L Lucats ◽  
M P Pruniaux ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Healthy Volunteers ◽  
Chronic Treatment ◽  
Positive Inotropic Effect ◽  
Post Myocardial Infarction ◽  
Inotropic Effect ◽  
Reduced Ejection Fraction ◽  
Omecamtiv Mecarbil

Abstract Background Omecamtiv mecarbil (OM), a novel myosin ATPase activator, is currently developed for the treatment of Heart Failure with reduced Ejection Fraction (HFrEF). Phase I in healthy volunteers and patients showed that the positive inotropic effect of OM was associated with an impairment of diastolic function as assessed by change in E peak, e' wave and E/e' ratio. Purpose The diastolic impact of chronic treatment with OM has not been described yet. This study investigates the balance between positive inotropic effect and the diastolic impairment after chronic treatment with OM in a post-myocardial infarction (Post-MI) swine model of HFrEF. Methods HFrEF was induced in minipigs after myocardial infarction caused by a 150-min left anterior descending (LAD) artery occlusion performed under angiography. HFrEF minipigs were treated with OM at 3 mg/kg PO BID for 15 days (n=4), a dose known to increase systolic ejection time (SET) by ∼50 ms as achieved in healthy volunteers and patients at plasma levels between 200–300 ng/ml. Echocardiogram was performed before and after 15 days of treatment with OM. An additional echocardiogram was conducted 7 days after the last administration. Results One year after MI, minipigs displayed increased left ventricular end-diastolic volume index (LVEDVi 151±3.7ml/m2 vs 100±8.9ml/m2 before infarction) and decreased LVEF (42±2.5% vs 68±4.4% before infarction) associated with a pseudo-normal mitral pattern. A two-week treatment with OM increased SET by 64ms (p<0.0001 vs before treatment) and EF to 49±3.8% (p=0.07 vs before treatment) as well as it improved SVi by 13%. This inotropic effect was associated with a decrease of mitral E peak (p=0.01 vs before treatment) and e' waves, and with the prolongation of deceleration time (p<0.05 vs before treatment). OM treatment was associated with marked reduction of LVEDVi to 117±13.2ml/m2 (p<0.05 vs before treatment) concomitant with a ∼20% increase in diastolic septum and posterior wall thicknesses. None of these systolic or diastolic effects remained 7 days post OM treatment completion. Conclusion Similarly to clinical description, OM treatment increased LVEF and SVi principally through extension of SET. It provides positive inotropic effects associated with diastolic impairment resulting in impaired ventricular filling as assessed by LVEDVi decrease and the thickening of ventricular wall in diastole. Whether this profile will allow a beneficial reverse remodeling, needs to be investigated in a longer chronic study. Acknowledgement/Funding Sanofi sponsored study

Abstract 17371: In-Hospital Outcomes of Ablation for Ventricular Tachycardia in Heart Failure With Reduced Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Raj Patel ◽  
Dipesh Ludhwani ◽  
Harsh P Patel ◽  
Samarthkumar J Thakkar ◽  
Love shah ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Tachycardia ◽  
Catheter Ablation ◽  
Ejection Fraction ◽  
Reference Group ◽  
Coronary Bypass ◽  
Reference Population ◽  
Reduced Ejection Fraction ◽  
Vt Ablation

Introduction: Ventricular tachycardia (VT) is a significant cause of morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). Hypothesis: Data on efficacy, safety, and outcomes of catheter ablation for VT in HFrEF have not been studied well. Methods: The 2002-2014 Nationwide Inpatient Sample (NIS) was used to identify all hospitalizations with a principle diagnosis of VT (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code 427.1) and a secondary diagnosis of HFrEF. Patients who underwent catheter ablation were identified using ICD-9-CM procedure code 37.34. Results: Of 228,557 patients with HFrEF & VT, 5845 (2.56%) underwent catheter ablation. The prevalence of Diabetes Mellitus (DM) and Chronic Kidney disease (CKD) was higher in the reference population contrary to a higher prevalence of prior myocardial infarction (MI), coronary bypass and AICD in those undergoing CA. The frequency of complications in the ablation group was 19.47%, the most common being post-operative hemorrhage (8.3%). This was followed by myocardial infarction (5.34%), pericardial complications (3.38%), and neurological complications (2.14%) (Figure 1.). The odds of in-hospital mortality were lower in the CA group compared to the reference group (5.08% vs 9.42%, p<0.05). Conclusions: Compared to medical therapy, VT ablation in HFrEF is associated with lower mortality though with significant complication rate. This suggests a need for future studies identifying the safety measures in VT ablations and instituting appropriate interventions to improve overall VT ablation outcomes.

scholarly journals Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction

2020 ◽  
Vol 8 (4) ◽  
pp. 329-340 ◽  
Author(s):  
John R. Teerlink ◽  
Rafael Diaz ◽  
G. Michael Felker ◽  
John J.V. McMurray ◽  
Marco Metra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Omecamtiv Mecarbil

scholarly journals Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
G. Michael Felker ◽  
Scott D. Solomon ◽  
John J.V. McMurray ◽  
John G.F. Cleland ◽  
Siddique A. Abbasi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Symptom Score ◽  
Summary Score ◽  
Total Symptom Score ◽  
Reduced Ejection Fraction ◽  
Related Quality ◽  
Health Related ◽  
Omecamtiv Mecarbil

Background: Chronic heart failure with reduced ejection fraction impairs health-related quality of life (HRQL). Omecamtiv mecarbil (OM)—a novel activator of cardiac myosin—improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms and HRQL in patients with chronic heart failure with reduced ejection fraction and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure). Methods: Patients (n=448) were randomized 1:1:1 to placebo, 25 mg of OM BID, or to pharmacokinetically guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score, Physical Limitation Scale, and Clinical Summary Score. Results: Mean change in score from baseline to 20 weeks for the Total Symptom Score was 5.0 (95% CI, 1.8–8.1) for placebo, 6.6 (95% CI, 3.4–9.8) for OM 25 mg ( P =0.32 versus placebo), and 9.9 (95% CI, 6.7–13.0) for OM-PK ( P =0.03 versus placebo); for the Physical Limitation Scale, it was 3.1 for placebo (95% CI, −0.3 to 6.6), 6.0 (95% CI, 3.1–8.9) for OM 25 mg ( P =0.12), and 4.3 (95% CI, 0.7–7.9) for OM-PK ( P =0.42); for the Clinical Summary Score, it was 4.1 (95% CI, 1.4–6.9) for placebo, 6.3 (95% CI, 3.6–9.0) for OM 25 mg ( P =0.19), and 7.0 (95% CI, 4.1–10.0) for OM-PK ( P =0.14). Differences between OM and placebo were greater in patients who were more symptomatic at baseline. Conclusions: HRQL as measured by the Total Symptom Score improved in patients with heart failure with reduced ejection fraction assigned to the OM-PK group relative to placebo. Ongoing trials are prospectively testing whether OM improves symptoms and HRQL in heart failure with reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01786512.

scholarly journals Plasma renin activity in patients with heart failure and reduced ejection fraction on optimal medical therapy

2017 ◽  
Vol 18 (3) ◽  
pp. 147032031772991 ◽  
Author(s):  
Petra Nijst ◽  
Frederik H Verbrugge ◽  
Pieter Martens ◽  
Philippe B Bertrand ◽  
Matthias Dupont ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Plasma Renin Activity ◽  
Healthy Volunteers ◽  
Cardiovascular Mortality ◽  
Plasma Renin ◽  
Renin Activity ◽  
Prognostic Impact ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction

Background: Renin-angiotensin-aldosterone system (RAAS) activation in heart failure with reduced ejection fraction (HFREF) is detrimental through promotion of ventricular remodeling and salt and water retention. Aims: The aims of this article are to describe RAAS activity in distinct HFREF populations and to assess its prognostic impact. Methods: Venous blood samples were prospectively obtained in 76 healthy volunteers, 72 patients hospitalized for acute decompensated HFREF, and 78 ambulatory chronic HFREF patients without clinical signs of congestion. Sequential measurements were performed in patients with acute decompensated HFREF. Results: Plasma renin activity (PRA) was significantly higher in ambulatory chronic HFREF (7.6 ng/ml/h (2.2; 18.1)) compared to patients with acute decompensated HFREF (1.5 ng/ml/h (0.8; 5.7)) or healthy volunteers (1.4 ng/ml/h (0.6; 2.3)) (all p < 0.05). PRA was significantly associated with arterial blood pressure and renin-angiotensin system blocker dose. A progressive rise in PRA (+4 ng/ml/h (0.4; 10.9); p < 0.001) was observed in acute decompensated HFREF patients after three consecutive days of decongestive treatment. Only in acute HFREF were PRA levels associated with increased cardiovascular mortality or HF readmissions ( p = 0.035). Conclusion: PRA is significantly elevated in ambulatory chronic HFREF patients but is not associated with worse outcome. In contrast, in acute HFREF patients, PRA is associated with cardiovascular mortality or HF readmissions.

Abstract MP85: Prognostic Impact of Heart Failure with Preserved and Reduced Ejection Fraction after Myocardial Infarction in the Community

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Yariv Gerber ◽  
Susan A Weston ◽  
Cecilia Berardi ◽  
Alanna M Chamberlain ◽  
Sheila M McNallan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Early Onset ◽  
Late Onset ◽  
Secular Trends ◽  
Prognostic Impact ◽  
Reduced Ejection Fraction ◽  
Risk Of Death

Background: Contemporary community data on the prognostic importance of heart failure (HF) after myocardial infarction (MI) according to (1) preserved or reduced ejection fraction (EF) and (2) the time of its occurrence are lacking. We examined HF-associated mortality and secular trends in survival among patients with and without HF in a geographically defined cohort of MI survivors. Methods: All residents of Olmsted County, Minnesota (n=2,596) who had a first MI diagnosed in 1990-2010 and no prior HF were followed through 2012 for HF incidence and mortality. Framingham Heart Study criteria were used to define HF, which was further classified according to EF. Cox models were used to examine (1) the hazard ratios (HRs) for death associated with HF type (preserved or reduced) and timing (early- or late-onset); and (2) secular trends in survival by HF status. Results: During a mean (SD) follow-up of 4 (3) years, 748 patients developed HF (519 within 30 days) and 673 died. After adjusting for age, sex, and year of index MI, HF as a time-dependent variable was strongly associated with mortality (HR=3.33 vs. HF-free subjects). Mortality did not differ by HF type, but was markedly higher for late-onset (>30 days) than for early-onset HF. Further adjustment for indicators of MI severity and comorbidity burden, acute intervention, and recurrent MI attenuated the association (Table). The age- and sex-adjusted HRs for mortality in 2001-2010 vs. 1990-2000 were 0.71 (95% CI: 0.58-0.88) in HF and 0.74 (95% CI: 0.59-0.93) in HF-free patients. These estimates equate to 10.18 (95% CI: 3.82-16.54) and 3.75 (95% CI: 0.90-6.61) fewer deaths per 100 subjects at 5 years of follow-up in participants with and without HF, respectively. Conclusions: HF markedly increases the risk of death after MI. The magnitude of this excess risk is similar between preserved and reduced EF but greater for late- vs. early-onset HF. Mortality declined over time in all patients with MI, and the absolute reduction in the risk of death was substantially greater for those with HF.

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