Lithuanian Echocardiography Study of Dyspnea in Acute Settings (LEDA)

November 20, 2018 updated by: Jelena Čelutkienė, Vilnius University

Diagnostic and Prognostic Value of Cardiac Biomarkers and Echocardiography for Patients Hospitalized Due to Acute Dyspnea: Prospective Observational Multicenter Cohort Study

LEDA (Lithuanian Echocardiography study of Dyspnea in Acute settings) is a prospective observational cohort multicenter clinical study. Project is carried out by Vilnius University together with a partner Lithuanian University of Health Sciences, in conjunction with a research protocol of international GREAT consortium (Global Research on Acute Conditions Team). The aim of this project is to find the specific novel biomarkers of acute heart failure (AHF), to evaluate their diagnostic and prognostic role in association with echocardiographic parameters of AHF. Primary endpoint is 1-year all-cause mortality and rehospitalization. Secondary endpoints are 1) in-hospital all-cause mortality 2) post-discharge 1 and 3 month all-cause mortality and rehospitalization 3) post-discharge 1 and 3 month cardiovascular mortality and rehospitalization 4) one-year cardiovascular mortality and rehospitalization.

During the project a sizeable national database (2000 Lithuanian patients) will be integrated into database of GREAT network. Novel cardiac biomarkers together with ultrasound parameters of right ventricular (RV) function are in the focus of the study. During the acute phase of heart failure, up to 15 novel cardiac, vascular, renal impairment and inflammation biomarkers in plasma samples will be investigated in Lithuania and France (INSERM laboratory). Plasma samples will be taken during 4 hours after admission and frozen at -80ºC to allow batch analysis. The extensive evaluation of innovative ultrasound parameters of right ventricular structure and function will be performed in the early hospitalization period, along with standard echocardiography examination. The first database of AHF patients in Lithuania will provide demographic data and trends of morbidity and mortality, as well as analysis of diagnostic and prognostic value of novel biomarkers and echocardiography parameters in the Baltic region. Quantitative parameters of RV systolic function and deformation will be measured. It is expected that optimal use of novel biomarkers and reproducible echocardiography parameters in the setting of emergency and critical care would reduce unnecessary hospitalizations, cost and hospital length of stay without decrease in the quality of diagnostics and treatment. An estimation of correlation of echocardiographic parameters and biomarkers could help create an accurate algorithm for risk stratification and diagnosis of AHF in an emergency setting.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Heart failure (HF) is believed to be the modern-day epidemic due to increasing incidence, impaired long-term prognosis and huge economic burden. With the ageing population the impact of HF on health care resources is on the rise. The course of the disease is characterized by episodes of acute decompensation that mark a significant turning point in the progress of the disease, with in-hospital mortality rates as high as 10%. Acute heart failure (AHF) is a gradual or rapid change in HF signs and symptoms, requiring urgent medical therapies. Acute heart failure is estimated to be the most costly and the most frequent cause of admission to emergency wards. Emergency department (ED) is the primary setting where initial AHF management takes place. However, strong evidence for diagnostics and management of this grave condition is still lacking. Even less is known about the prevalence, diagnosis and management of acute right ventricular failure (RVF).

A patient presenting to the ED with acute dyspnea has to undergo numerous procedures in order to differentiate the diagnosis between AHF, chronic obstructive pulmonary disease, pneumonia, pulmonary embolism and other etiologies. Moreover, the majority of HF patients suffer from comorbidities that make the diagnostic process even more challenging. Due to numerous exams and tests, the initial management of these patients may be delayed, resulting in an extended hospital length of stay, increased rate of complications and death. The clinical, hemodynamic and neurohormonal features of heart failure are different in specific patient populations and depend on age, sex, race, left ventricular ejection fraction and co-existent right ventricular (RV) dysfunction as well as many other factors.

Cardiac biomarkers are easily reproducible and objective laboratory tests that could help to improve early AHF diagnosis and risk stratification. However, reported data suggest varying prognostic and diagnostic values of natriuretic peptides, such as N-type natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), MR pro-atrial natriuretic peptide (MR-proANP), as well as regional differences of these markers. Specific biomarkers of RVF have not yet been described, thus a search of novel serologic markers that could rapidly and reliably help diagnose acute RVF is a very important scientific task in cardiology. Furthermore, the knowledge on the incidence of RVF syndrome as well as the diagnostic and prognostic values of ultrasound RV structural and functional parameters is scarce. During this study the RV-focused ultrasound examination will be performed in the early hospitalization period, and blood samples will be taken and frozen at the same time. Up to 15 novel cardiac, vascular, renal impairment and inflammation biomarkers in plasma samples during acute phase of RVF will be investigated during the study in France, INSERM laboratory. The study will be unique as it will aggregate large scale observational and biomarkers database of AHF patients in Lithuania together with innovative ultrasound parameters of RV failure (quantitative parameters of RV systolic function and deformation).

The aim of this project is to find the specific novel biomarkers of acute heart failure (AHF), to evaluate their diagnostic and prognostic role in association with echocardiographic parameters of AHF.

The primary endpoint is 1-year all-cause mortality and rehospitalization.

Secondary endpoints are:

  1. in-hospital all-cause mortality
  2. post-discharge 1 and 3 months all-cause mortality and rehospitalization
  3. post-discharge 1 and 3 months cardiovascular mortality and rehospitalization
  4. one-year cardiovascular mortality and rehospitalization.

Objectives of this project are:

  1. To create a database of patients hospitalized due to acute heart failure in Lithuania, integrated to GREAT (Global Research on Acute Conditions Team) network database;
  2. To compare the diagnostic and prognostic value of novel cardiac, vascular, renal insufficiency and inflammation biomarkers in the Lithuanian patient cohort to other countries in the GREAT network;
  3. To determine the demographic, clinical and treatment characteristics as well as short and long term outcome of patients hospitalized due to AHF in Lithuania and other GREAT network countries;
  4. To evaluate the epidemiology of RVF together with clinical features and outcome of patients in a cohort of Lithuanian acute heart failure (HF) patients;
  5. To estimate a correlation between ultrasound parameters of RV structure and function and novel cardiac, vascular, renal and inflammation biomarkers in acute period of HF;
  6. To identify novel ultrasound parameters of RV structure and function parameters and biomarkers predicting a risk of 1 year mortality after hospitalization;
  7. To create an algorithm of RV failure diagnostics and risk stratification based on the diagnostic and prognostic value of detected echocardiographic parameters and biomarkers.

Observational studies and recent meta-analyses indicate that in acute conditions RVF may be as frequent as let ventricular failure (LVF) and is associated with markedly poor prognosis. Largely empiric knowledge in emergency medicine suggests that right and left ventricular failure requires different therapeutic approaches, including disparate principles of intravenous treatment, due to distinct hemodynamic impairment. The outcome of RVF is largely dependent on the underlying cause, resulting in either an acute or chronic presentation.

Novel biomarkers can help identify the underlying conditions in AHF. These include myocardial injury markers such as copeptine, proenkephalin, high sensitivity troponin T, troponin I, brain natriuretic peptide (BNP), N-terminal-proBNP; renal and hepatic involvement markers such as adrenomedullin, neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid binding protein (L-FABP), galectin-3, soluble ST2, cystatin C; inflammatory markers such as C-reactive protein, interleukine 6, procalcitonin. These markers could help evaluate end-organ involvement, as well as the extent of myocardial remodeling, and in return provide state-of-the-art tailored patient care. Specific biomarkers of RV involvement or dysfunction have not yet been described, therefore identification of such biomarkers would allow to accelerate the diagnosis of RVF and initiate specific treatment.

Echocardiography is a potent and accessible technique for the diagnosis of AHF in an acute setting. Echocardiography also provides information about the mechanisms of AHF as well as alternative causes of dyspnea. Echocardiographic parameters of RV structure and function are of particular interest since not much data is available on acute RVF. Quantitative parameters of RV systolic and diastolic function, RV wall deformation or notional hemodynamic parameters could potentially be useful for diagnosis and selection of urgent treatment tactics. In the current literature there are no publications about the diagnostic and prognostic value of RV parameters, especially about novel echocardiographic parameters (strain rate, speckle tracking), in the early phase of exacerbated heart failure.

Global Research on Acute Conditions Teal (GREAT) Association is an international network among experts operating in the management of acute clinical conditions in the field of emergency medicine and doing research through the concept of translational medicine. This network integrates research inputs from basic sciences and interventional epidemiology to optimize both patient care and preventive measures. Moreover, one of the main objectives of the GREAT association is to standardize the clinical and organizational system approach in acute conditions disease management all over the world, with the concept of globalization medicine. Up to this day there has not been any large multicenter observational and biomarkers studies in Lithuania in the field of AHF. Our study creates a unique opportunity to join the worldwide GREAT network and its patient database, that could potentially contain up to 50 000 patients.

Study Type

Observational

Enrollment (Actual)

1566

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Ile De France
      • Paris, Ile De France, France, 75475
        • Inserm U942
  • Lithuania
      • Kaunas, Lithuania, 50009
        • Lithuanian University of Health Sciences
      • Vilnius, Lithuania, 08406
        • Vilnius University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Adult patients (18 years and older) who present to the hospital (Vilnius University hospital Santariškių Klinikos and Hospital of Lithuanian University of Health Sciences Kauno Klinikos) due to acute dyspnea. Besides acute heart failure, patients with pulmonary causes of dyspnea as well as pulmonary embolism, acute infections, cancer and other reasons are enrolled. Patients admitted to the ward as well as and discharged home from the emergency department are enrolled.

Description

Inclusion Criteria:

  • presentation to hospital with acute dyspnea.

Exclusion Criteria:

  • refusal to give informed consent; acute coronary syndromes.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Acute heart failure patients
Adult patients (18 years and older) who are admitted to the emergency department (Vilnius University Hospital Santariškių Klinikos and Hospital of Lithuanian University of Health Sciences Kauno Klinikos) due to acute dyspnea and have an adjudicated diagnosis of acute heart failure. Blood sampling and echocardiography examination will be performed.
Procedure: Blood sampling
Besides routine clinical, laboratory and instrumental evaluation, blood samples will be taken within 4 hours of presentation to the hospital. Plasma samples, stored and frozen at -80°C, will be analyzed at the INSERM UMR942 institute in Paris. Up to 15 novel will be measured during the study: copeptine, proenkephalin, high sensitivity troponin T, troponin I, brain natriuretic peptide (BNP), N-terminal pro-BNP, adrenomedullin, soluble ST2, galectine 3, C-reactive protein, interleukine 6, procalcitonin, cystatin C, neutrophil gelatinase associated lipocalin.
Procedure: Echocardiography exam
A standard echocardiography as well as examination focused on right ventricle (RV) will be performed in a period of 48 hours of admission. Novel qualitative and quantitative parameters of right ventricle function and structure will be measured. These include RV diameter at base and midlevel, a measure of RV fractional area change (FAC), tissue doppler imaging derived tricuspid lateral annular systolic velocity wave (S'), tricuspid annular plane systolic excursion (TAPSE), velocity and gradient of tricuspid regurgitation, estimated systolic RV and RA pressure, RV wall strain and strain rate.
Control group
Patients who are admitted to the emergency departments of participating centers due to acute dyspnea with an adjudicated diagnosis other than heart failure (pulmonary causes of dyspnea such as pulmonary embolism, acute infections, cancer and other reasons). Blood sampling and echocardiography examination will be performed.
Procedure: Blood sampling
Besides routine clinical, laboratory and instrumental evaluation, blood samples will be taken within 4 hours of presentation to the hospital. Plasma samples, stored and frozen at -80°C, will be analyzed at the INSERM UMR942 institute in Paris. Up to 15 novel will be measured during the study: copeptine, proenkephalin, high sensitivity troponin T, troponin I, brain natriuretic peptide (BNP), N-terminal pro-BNP, adrenomedullin, soluble ST2, galectine 3, C-reactive protein, interleukine 6, procalcitonin, cystatin C, neutrophil gelatinase associated lipocalin.
Procedure: Echocardiography exam
A standard echocardiography as well as examination focused on right ventricle (RV) will be performed in a period of 48 hours of admission. Novel qualitative and quantitative parameters of right ventricle function and structure will be measured. These include RV diameter at base and midlevel, a measure of RV fractional area change (FAC), tissue doppler imaging derived tricuspid lateral annular systolic velocity wave (S'), tricuspid annular plane systolic excursion (TAPSE), velocity and gradient of tricuspid regurgitation, estimated systolic RV and RA pressure, RV wall strain and strain rate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1-year all-cause mortality and rehospitalization
Time Frame: 1 year
The sum of all-cause deaths and all-cause rehospitalizations in AHF and non-AHF groups
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
In-hospital all-cause mortality
Time Frame: 28 days
All-cause deaths before discharge in AHF and non-AHF groups
28 days
Post-discharge all-cause mortality and rehospitalization
Time Frame: 1 and 3 months
The sum of all-cause deaths and all-cause rehospitalizations in AHF and non-AHF groups in 1 and 3 months minus Outcome 2
1 and 3 months
Post-discharge cardiovascular mortality and rehospitalization
Time Frame: 1 and 3 months
The sum of cardiovascular deaths and cardiovascular rehospitalizations in AHF and non-AHF groups in 1 and 3 months minus Outcome 2
1 and 3 months
1-year cardiovascular mortality and rehospitalization
Time Frame: 1 year
The sum of cardiovascular deaths and cardiovascular rehospitalizations in AHF and non-AHF groups
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prognostic role of circulating biomarkers
Time Frame: 1 year
Hazard ratio and odds ratio of NT-proBNP, GDF-15 and troponin for primary and secondary outcomes
1 year
Prognostic role of echocardiographic parameters
Time Frame: 1 year
Hazard ratio and odds ratio of TAPSE, LVEF, RV strain for primary and secondary outcomes
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vilnius University

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France
Lithuanian University of Health Sciences

Investigators

  • Study Chair: Jelena Celutkiene, Professor, Vilnius University
  • Principal Investigator: Ausra Kavoliuniene, Professor, Lithuanian University of Health Sciences
  • Principal Investigator: Alexandre Mebazaa, Professor, INSERM, BIOmarkers in CArdioNeuroVAScular diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 1, 2015

Primary Completion (ACTUAL)

December 1, 2017

Study Completion (ACTUAL)

November 1, 2018

Study Registration Dates

First Submitted

February 2, 2017

First Submitted That Met QC Criteria

February 7, 2017

First Posted (ESTIMATE)

February 9, 2017

Study Record Updates

Last Update Posted (ACTUAL)

November 23, 2018

Last Update Submitted That Met QC Criteria

November 20, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MIP-049/2015 (OTHER_GRANT: Research Council of Lithuania)
  • L-15-01/1 (OTHER: Lithuanian Bioethics Commitee)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data will be made available to other researchers via GREAT (Global REsearch on Acute Conditions Team) database

IPD Sharing Time Frame

2019-2024

IPD Sharing Access Criteria

referral to prof. A. Mebazaa

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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