Lithuanian Echocardiography Study of Dyspnea in Acute Settings
Lithuanian Echocardiography Study of Dyspnea in Acute Settings
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.
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.
Inclusion Criteria:

 -  presentation to hospital with acute dyspnea.

 Exclusion Criteria:

 -  refusal to give informed consent; acute coronary syndromes.