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

NCT ID: NCT04397302

Last Updated: 2020-05-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 652 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-13
• Study Completion Date: 2020-03-16

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).

Conditions

Heart Failure, Left Sided; Left Ventricular Dysfunction; Ventricular Remodeling

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

Role of Sacubitril/Valsartan in Hemodynamic and Echocardiographic Improvement of Heart Failure With Reduced Ejection Fraction

Reverse Remodeling is Associated With Hemodynamic Improvement and Stabilization in Outpatients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan: an Echocardiographic Study

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Ambulatory patients on stable optimal medical therapy
• History of HF and LVEF ≤ 40%
• II-III NYHA class

Exclusion Criteria

• History of congenital heart disease
• Severe valvular disease or valvular surgery
• Recent acute coronary syndromes or stroke
• Poor acoustic windows or missing data.
• Death or uncompleted follow-up evaluation
• Cardiac surgery interventions
• Cardiac resynchronization therapy
• Coronary or mitral interventions

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università degli Studi di Brescia

OTHER

Sponsor Role: collaborator

Federico II University

OTHER

Sponsor Role: collaborator

Ospedali Riuniti di Foggia

OTHER

Sponsor Role: collaborator

University Of Perugia

OTHER

Sponsor Role: collaborator

Monaldi Hospital

OTHER

Sponsor Role: collaborator

University of Messina

OTHER

Sponsor Role: collaborator

University of Siena

OTHER

Sponsor Role: collaborator

University of Salerno

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: collaborator

Azienda Ospedaliero-Universitaria di Parma

OTHER

Sponsor Role: collaborator

Azienda Unita Sanitaria Locale di Piacenza

OTHER

Sponsor Role: collaborator

Italian Society of Cardiology

OTHER

Sponsor Role: lead

Responsible Party

Frank Lloyd Dini, MD

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frank L Dini, MD

Role: PRINCIPAL_INVESTIGATOR

Italian Society of Cardiology

Locations

Frank Lloyd Dini

Pisa, , Italy

Countries

Italy

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Other Identifiers

20190015213

Identifier Type: -

Identifier Source: org_study_id