Role of Sacubitril/Valsartan in the Improvement of Heart Failure With Reduced Ejection Fraction

Completed

• Conditions: Heart Failure, Left Sided; Left Ventricular Dysfunction; Ventricular Remodeling

• Registration Number: NCT04397302
• Lead Sponsor: Italian Society of Cardiology

Brief Summary

This prospective study evaluates the mechanisms of benefit of sacubitril/valsartan in a population of outpatients with heart failure with reduced ejection fraction, to investigate the relationship between the effects on left ventricular ejection fraction and volumes and noninvasively hemodynamic echo-derived parameters, as cardiac output and left ventricular filling pressure.

Detailed Description

Therapeutic interventions were made according to a titration protocol in stable optimal medical therapy. Therapy with sacubitril/valsartan was introduced after a 48-hour wash-out of an ACE inhibitor or after a 24-hour wash-out of an angiotensin receptor antagonist. Doses of sacubitril/valsartan were optimized to individual tolerability.

Echocardiography was performed at baseline and after 12 months. LV end-diastolic and end-systolic volumes were calculated according to the biplane Simpson's method according to the recommendations of the American Society of Echocardiography and European Association of Cardiovascular Imaging. Doppler examinations included assessment of early diastolic filling velocity and early diastolic mitral annular velocity, an averaged E/e' ≥ 13 was considered a surrogate marker of increased filling pressure.

The LV stroke volume was calculated as the product of the LV outflow tract area and the time-velocity integral of the aortic flow velocity or was evaluated as the difference between LVEDV and LVESV. The LVSV index was estimated as LVSV divided by body surface area. Cardiac output (CO) was measured as stroke volume times heart rate, and the cardiac index was estimated by dividing CO by body surface area.

Patients who presented reverse remodeling were considered those exhibiting a ≥ 10% increase in ejection fraction and ≥15% reduction in end-systolic volume compared to baseline.

The accuracy of the sources data was verified by using in-hospital medical records, computerized or paper, by checking data from ultrasound images, laboratory reports or ambulatory cardiological tests.

Detailed information on patients' medical history, including medications and loop diuretic doses, was recorded for each patient. Patients' functional status was determined according to the classification of the New York Heart Association. Creatinine, B-type natriuretic peptide and amino-terminal pro-type B-natriuretic peptide levels were measured using standard laboratory methods. The estimated glomerular filtration rate was calculated by the Modification of Diet in Renal Disease formula.

Patients were removed from therapy with sacubitril/valsartan or assessment for non-adherence to treatment or persistent drug-related adverse event with his/her willingness to discontinue treatment.

Continuous measures were expressed as the mean value ± SD or median and interquartile range (IRQ) for normally and non-normally distributed variables, respectively. Continuous data were compared using paired and independent samples Student t-test or ANOVA when appropriate. Categorical variables were presented as percentages and were compared using Chi-square or McNemar test. Mann-Whitney, Kruskal-Wallis and Wilcoxon tests were used to analyze non-normally distributed variables. All differences were considered significant at the p = 0.05 level. Data were analyzed with SPSS version 23.0 (IBM Corp., Armonk, NY).

Study Timeline

• Study Start: 2019-01-13
• Primary Completion: 2020-03-16
• Study Completion: 2020-03-16
• Status Verified: 2020-05
• Study First Submitted: 2020-05-04
• Study First Submitted QC: 2020-05-17
• Study First Posted: 2020-05-21
• Last Update Submitted: 2020-05-26
• Last Update Posted: 2020-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 652

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change from baseline in Cardiac Output after 12 months of treatment	March, 16 th 2019 - March,16th 2020	Cardiac Output (in L/min) is a variable measured by echocardiography as the product of LV stroke volume (in mL/beat) and heart rate (in bpm).

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Left Ventricular Filling Pressure after 12 months of treatment	March, 16th 2019 - March,16th 2020	Left ventricular filling pressure is calculated by Doppler Echocardiography as the ratio of early diastolic filling velocity (E wave, m/s) and early diastolic mitral annular velocity (e', m/s). The increase of this ratio is indicative of higher LV filling pressure.

Trial Locations

Locations (1)

Frank Lloyd Dini; 🇮🇹 Pisa, Italy