Dataset Information

Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling.

ABSTRACT:

Aims

In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic, and sympatholytic effects.

Methods

We designed a randomized, double-blinded, active-comparator trial to examine the effect of sacubitril/valsartan to the current standard of care in reducing adverse LV remodelling in patients with asymptomatic LVSD following MI. Eligible patients were ?3 months following MI, had an LV ejection fraction ?40% as measured by echocardiography, were New York Heart Association functional classification I, tolerant of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at equivalent dose of ramipril 2.5 mg twice daily or greater, and taking a beta-blocker unless contraindicated or intolerant. Patients were randomized to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). The primary endpoint will be change in LV end-systolic volume indexed for body surface area measured using cardiac magnetic resonance imaging over 52 weeks from randomization. Secondary endpoints include other magnetic resonance imaging-based metrics of LV remodelling, biomarkers associated with LV remodelling and neurohumoral activation, and change in patient well-being assessed using a patient global assessment questionnaire.

Conclusions

This trial will investigate the effect of neprilysin inhibition on LV remodelling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.

SUBMITTER: Docherty KF

PROVIDER: S-EPMC7835504 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling.

Docherty Kieran F KF Campbell Ross T RT Brooksbank Katriona J M KJM Godeseth Rosemary L RL Forsyth Paul P McConnachie Alex A Roditi Giles G Stanley Bethany B Welsh Paul P Jhund Pardeep S PS Petrie Mark C MC McMurray John J V JJV

ESC heart failure 20201210 1

<h4>Aims</h4>In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic, and sympatholytic effect ...[more]

PMID: 33305513

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Project description:BackgroundPatients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects.MethodsWe performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire.ResultsFrom July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2-7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, -1.9 mL/m2 (95% CI, -4.9 to 1.0); P=0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change.ConclusionsIn patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.

Project description:The angiotensin-receptor-neprilysin inhibitor (ARNI) reduced cardiovascular deaths and heart failure hospitalization in patients with heart failure of reduced ejection fraction (HFrEF). Its role in non-HFrEF patients was not clear. This study aims to answer this question.In this retrospective study, we enrolled 928 patients diagnosed with non-HFrEF, 492 of them received angiotensin converting enzyme inhibitor (ACEI) and the rest 436 received angiotensin-receptor-neprilysin inhibitor. Outcomes were compared by Kaplan-Meier survival analysis and various clinical parameters were investigated using Cox multivariable analysis, followed by interaction analysis. Minnesota living with heart failure Questionnaire (MLHFQ) was employed as one of the criteria to assess heart failure outcome.The cardiovascular (CV) death or HF hospitalization at 24 months occurred in 49 patients in ACEI group compared with 31 in ARNI group (Hazard Ratio (HR): 1.231, 95% confidence Interval (CI): 1.080-2.460, P = .031). And ARNI showed better prognosis of HF hospitalization (HR: 1.283, 95%CI: 1.065-1.360, P = .038). Cumulative Kaplan-Meier estimates of endpoints, ARNI could reduce the incidence of CV death or HF hospitalization (P = .042) and HF hospitalization (P = .035). The stratified analysis revealed that participants with age less than 70 years old had a lower incidence of CV death or HF hospitalization (HR: 1.194, 95%CI: 1.011-1992, P = .031) after treated with ARNI. Patients received diuretics could benefit from ARNI (HR: 1.383, 95%CI: 1.082-1.471, P = .019). Similar results were also observed in patients with heart rate lower than 90 bpm (HR: 1.556, 95%CI: 1.045-2.386, P = .003) and patients with atrial fibrillation history (HR: 1.873, 95%CI: 1.420-2.809, P = .011). ARNI could improve the quality of life both from the total, emotional and physical aspects.ARNI is an efficacy treatment strategy to improve the outcome and quality of life in patients with non-HFrEF.

Project description:AimsThe purpose of this study is to identify echocardiography predictors of clinical response and reverse left ventricular (LV) remodelling in patients with functional mitral regurgitation (FMR) treated with MitraClip.Method and resultsWe retrospectively analysed 86 high surgical risk patients with severe FMR; of those, 58 were implanted a MitraClip, and 28 received medical treatment and served as controls. At baseline and at 1-year follow-up, we performed clinical and echocardiography evaluation to assess global longitudinal strain (GLS) and myocardial work [global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE)]. Mitral regurgitation was significantly reduced after MitraClip implantation (3.7 ± 0.4 vs. 1.7 ± 0.8, P < 0.001), and the procedure was associated with improvement in brain natriuretic peptide levels (980 ± 1027 vs. 420 ± 338 pg/mL, P < 0.001), New York Heart Association class status (3.2 ± 0.55 vs. 2.0 ± 0.6, P < 0.001), 6-min walking test (233 ± 154 vs. 286 ± 114 m, P = 0.01) at follow-up and reduction of left ventricle end-systolic (LVESV) and left ventricle end-diastolic volumes (LVEDV) (152 ± 68 vs. 136 ± 43 mL, P = 0.004 & 219 ± 74 vs. 193 ± 66 mL, P = 0.001, respectively). MitraClip procedure was associated with improvement of LV performance and significant increase of GWI (607 ± 282 vs. 650 ± 260 mmHg%, P = 0.045) and GCW (854 ± 288 vs. 949 ± 325 mmHg%, P < 0.001). Baseline ejection fraction (EF), GLS, GWI, GCW, and effective regurgitant orifice area were the variables that were associated with reduction of LVEDV 1 year after intervention (P < 0.05 for all) and baseline GCW of the LV was the only variable associated with reduction of LVESV (P = 0.002). Receiver operating characteristic curve analysis identified that a GLS cut-off value of -8.65% (AUC 0.815, P = 0.007) was associated with a 20% reduction of the LVEDV with a sensitivity and specificity of 72% and 70%, respectively, and that a GCW cut-off value of 846 mmHg% (AUC 0.759, P = 0.007) was associated with a 10% reduction of LVESV with sensitivity and specificity 79% and 74%, respectively.ConclusionsMitral valve repair with MitraClip has positive clinical and echocardiographic impact in patients with FMR 1 year after implantation. Preserved GLS and GCW values appear to be associated with LV reverse remodelling post intervention.

Dataset Information

Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling.

Aims

Methods

Conclusions

Publications

Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling.

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