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

Left Ventricular Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04397302
• Other study ID #: 20190015213
• Status: Completed
• Start date: January 13, 2019
• Est. completion date: March 16, 2020

Study information

• Verified date: May 2020
• Source: Italian Society of Cardiology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 652
• Est. completion date: March 16, 2020
• Est. primary completion date: March 16, 2020
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Diagnostic Test:
• 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

Locations

Country	Name	City	State
Italy	Frank Lloyd Dini	Pisa

Sponsors (12)

Lead Sponsor	Collaborator
Italian Society of Cardiology	Azienda Ospedaliero-Universitaria di Parma, Azienda Unità Sanitaria Locale di Piacenza, Federico II University, Monaldi Hospital, Ospedali Riuniti di Foggia, Policlinico San Matteo Pavia Fondazione IRCCS, Università degli Studi di Brescia, University of Messina, University Of Perugia, University of Salerno, University of Siena

Country where clinical trial is conducted

Italy, 

References & Publications (22)

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in Left Ventricular Stroke Volume after 12 months of treatment	The LV stroke volume (in mL/beat) is obtained at echocardiography, as the product of the LV outflow tract area (cm2) and the time-velocity integral (cm) of the aortic flow velocity.	March, 16th 2019 - March,16th 2020
Other	Change from baseline in Left Ventricular End-systolic Volume after 12 months of treatment	The LV End-systolic volume (in mL) is calculated according to the biplane Simpson's method according to the recommendations of the American Society of Echocardiography and European Association of Cardiovascular Imaging.	March, 16th 2019 - March,16th 2020
Primary	Change from baseline in Cardiac Output after 12 months of treatment	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).	March, 16 th 2019 - March,16th 2020
Secondary	Change from baseline in Left Ventricular Filling Pressure after 12 months of treatment	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.	March, 16th 2019 - March,16th 2020