Multimarker Approach for Acute Dyspnea in Elderly Patients Admitted in the Emergency Department (READ-MA)

Elderly people constitute the largest proportion of emergency department (ED) patients, representing 12% of all ED admissions. The need for diagnostic tests or therapeutic interventions is much greater in this patient population. Cardiovascular diseases and symptoms represent 12% of the causes for ED admission, and patients suffering from cardiovascular disease are those whose ED visit lasts longest.

The diagnostic approach in the ED in elderly patients admitted for acute dypsnoea is complex, and early identification of acute left-sided heart failure (ALSHF) is vital as it has an impact on prognosis. The clinical signs are difficult to interpret, and are non-specific, particularly at the acute phase and in elderly or obese patients. Indeed, some authors have reported up to 50% of diagnostic errors in elderly patients.

Measure of the blood concentration of a natriuretic peptide allows a quick diagnosis. However, peptides alone suffer from several limitations, particularly in situations that are often encountered in elderly patients, such as sepsis, renal failure, acute coronary syndrome, pulmonary embolism, chronic respiratory failure, atrial fibrillation and high body mass index. Diagnostic performance deteriorates with increasing age, and there is a significant increase in this grey-zone in patients aged ≥75 years. In critical situations in elderly patients, assessment of natriuretic peptides serve mainly to rule out a diagnosis of left heart failure.

Some authors have studied other biomarkers showing their performance in the diagnosis of ALSHF. These are biomarkers involved in remodeling and myocardial fibrosis (ST2, Galectin-3) or involved in myocardial injury (High-sensitivity Troponin-I).

Therefore, a combined "multimarker" approach could improve the diagnostic performance of ALSHF.

READ (NCT02531542) is a diagnostic study including patients over the age of 75 admitted to acute dyspnea in the ED, to demonstrate the superiority of an ultrasound protocol (the READ protocol) on NT-proBNP in the ALSHF diagnosis.

The hypothesis is that the diagnostic accuracy of a multimarker diagnostic approach, namely the READ-MA method, combining NT-proBNP, High-sensitivity Troponin-I, ST2 and Galectin-3 would be superior to that of NT-proBNP assessment for the diagnosis of ALSHF in elderly patients (≥75 years) admitted to the ED.

Study Overview

• Status: Completed
• Conditions: Acute Heart Failure; Acute Dyspnea
• Intervention / Treatment: Diagnostic test: READ-MA Multimarker Approach

• Study Type: Observational
• Enrollment (Actual): 238

Contacts and Locations

Study Locations

• France
  • Franche-Comté
    • Besançon, Franche-Comté, France, 25000
      • CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All patients aged ≥75 years admitted to the ED for acute dyspnea

Description

Inclusion Criteria :

• Admission to the Emergency Department with age ≥ 75 years
• AND criteria of acute dyspnea :

Breathe rate ≥ 25 cycles/minute or PaO2 ≤ 70 mmHg or SpO2 ≤ 92% in room air or PacO2 ≥ 45 mmHg and pH ≤ 7.35

- AND Electrocardiogram in sinus rhythm or in atrial fibrillation at admission

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute Heart Failure	Diagnostic test: READ-MA Multimarker Approach; The presence or absence of ALSHF (gold standard used in the READ study) : diagnosis by 2 experts (cardiologist and emergency physician) based on data collected in the ED and during hospitalization (clinical examination, history, usual treatment, haemodynamic parameters, ECG, chest X-ray, emergency treatment, clinical and paraclinical results during hospitalization), biological assays (except NT-proBNP) and echocardiography (Left Ventricular Ejection Fraction, segmental kinetic, potential valvulopathy, transmitral flow, tissue doppler E' velocity) performed by a cardiologist within 24 hours of admission.
No Acute Heart Failure	Diagnostic test: READ-MA Multimarker Approach; The presence or absence of ALSHF (gold standard used in the READ study) : diagnosis by 2 experts (cardiologist and emergency physician) based on data collected in the ED and during hospitalization (clinical examination, history, usual treatment, haemodynamic parameters, ECG, chest X-ray, emergency treatment, clinical and paraclinical results during hospitalization), biological assays (except NT-proBNP) and echocardiography (Left Ventricular Ejection Fraction, segmental kinetic, potential valvulopathy, transmitral flow, tissue doppler E' velocity) performed by a cardiologist within 24 hours of admission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the diagnostic performance of the multimarker approach (combining NT-proBNP, High-sensitivity Troponin-I, ST2 and Galectin-3) for the diagnosis of ALSHF in patients aged ≥75 years admitted to the ED for acute dyspnea	The presence or absence of ALSHF (gold standard used in the READ study) : diagnosis by 2 experts (cardiologist and emergency physician) based on data collected in the ED and during hospitalization, biological assays (except NT-proBNP) and echocardiography performed by a cardiologist.; The positivity of the evaluated test (multi-marker approach) :For NT-proBNP, the threshold for positivity is higher than 1800 pg/mL. There is no consensus for High-Sensitivity Troponin-I, ST2 and Galectin-3. Firstly, the optimal threshold of each of these 3 biomarkers will be assessed by ROC curve, then the best combination between these 4 biomarkers will be tested to obtain an optimal discrimination (sensitivity, specificity positive and negative predictive values), positive and negative likelihood ratios) using various methods.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To demonstrate the superiority of the multimarker approach (NT-proBNP, High-sensitivity Troponin-I, ST2 and Galectin-3) over NT-proBNP alone for the diagnosis of ALSHF in patients aged ≥75 years admitted to the ED for acute dyspnea	To demonstrate the superiority of this combined multi-marker approach combining NT-proBNP, Troponin-I ultrasensitive, ST-2 and Galectin-3 on NT-proBNP alone in the diagnosis of ALSHF in subjects over 75 years admitted to emergencies for acute dyspnea, will be evaluated : The presence or absence of acute left heart failure (gold standard selected in the context of the READ study) will be determined using the previously defined criteria; The evaluated test will be the best multimarker approach previously determined, classified as positive or negative using the previously defined criteria; The comparative test (NT-proBNP alone) will be classified positive for a threshold higher than 1800 pg/mL	1 day

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Study Chair: Frédéric MAUNY, Prof, MD, PhD, CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON; Study Chair: Patrick RAY, Prof, MD, PhD, Centre Hospitalier Universitaire Dijon; Study Chair: Camille CHENEVIER-GOBEAUX, PharmD, PhD, Hôpital Cochin, Assistance Publique Hôpitaux de Paris; Study Chair: Marie-Hélène TOURNOYS, PharmD, Centre Hospitalier de Béthune; Study Chair: Noémie NMINEJ, CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON; Study Chair: Marc PUYRAVEAU, MSc, CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON; Study Chair: Alain-Eric DUBART, MD, CH Bethune

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 21, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Estimated): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Dyspnea
• Other Study ID Numbers: P/2019/466

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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