Hemodynamic Effects of ARNI on Noninvasive Pressure-volume Analysis in Patients With Chronic Heart Failure (ARNI-PVA)

Hemodynamic Effects of Angiotensin Receptor Neprilysin Inhibition on Noninvasive Pressure-volume Analysis in Patients With Heart Failure With Reduced Ejection Fraction

Sacubitril-Valsartan reduced heart failure hospitalizations and cardiovascular mortality compared to enelapril in chronic heart failure. Furthermore, quality of life is improved. The decrease of NT-proBNP levels during Sacubitril-Valsartan treatment is associated with reverse left ventricular remodeling and improved left ventricular systolic function. However, the underlying mechanisms that contribute to these symptomatic and prognostic benefits are largely unknown. The aim of this study is to evaluate left ventricular hemodynamics in patients treated with Sacubitril-Valsartan using non-invasive pressure-volume analysis.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Drug: Sacubitril-Valsartan

• Study Type: Observational
• Enrollment (Actual): 117

Contacts and Locations

Study Locations

• Germany
  • Kaiserslautern, Germany
    • Kardiopraxis Schirmer
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • University of Leipzig

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with symptomatic heart failure (NYHA functional class II to IV) and reduced ejection fraction (LVEF≤40%) with clinical indication for therapy with Sacubitril-Valsartan

Description

Inclusion Criteria:

• Symptomatic heart failure (NYHA functional class II to IV)
• Reduced LV ejection fraction (≤ 40%)
• Clinical indication for therapy with Sacubitril-Valsartan

Exclusion Criteria:

• catecholamine therapy at inclusion
• existing therapy with Sacubitril-Valsartan
• planned cardiac resynchronization therapy (CRT) within 6 months; inclusion at least 3 months after CRT
• planned mitral or aortic valve procedure within 6 months; inclusion at least 3 months after valve procedure
• participation in another randomized heart failure trial
• severe aortic or mitral valve lesion

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular contractility, afterload and ventricular-arterial coupling	Change of end-systolic elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic and diastolic LV function, symptom status and biomarkers	Echocardiography: Left ventricular (LV) remodeling und function (LVEDV, LVESV, LVEF, GLS), diastolic LV function (LAESV, E/e', LVEDP); Symptoms: NYHA functional class, 6 minute walk test; Biomarker: NT-proBNP	3, 6 and 12 months
Left ventricular contractility, afterload and ventricular-arterial coupling	Change of end-systolic elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees)	3 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Load-independent parameters of systolic and diastolic LV function, myocardial work indices	Peak power index (PPI); Preload-recruitable stroke work (PRSW); End-systolic meridional wall stress (EsMWS); Total peripheral resistance (TPR); LV end-systolic pressure (LVEDP); LV end-diastolic pressure-volume relationship (LVEDPVR); Pressure-strain loops	3, 6 and 12 months

Collaborators and Investigators

• Sponsor: University of Leipzig
• Investigators: Principal Investigator: Daniel Lavall, MD, University of Leipzig

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): April 8, 2026

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: DL-L-20005_V1.4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No