Clinical trial NCT02289508: Role of USCOM in Adult Patients With Heart Failure
Official title: Diagnostic and Prognostic Role of USCOM in Adult Patients With Heart Failure-A Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Decompensated Heart Failure
Congestive Heart Failure Compensated
Keywords: Heart Failure
Hemodynamics
Echocardiography
Diagnostic techniques and procedures
Ultrasonography
USCOM
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Cardiff and Vale University Health Board
name: University Hospitals, Leicester
First posted: 2014-11-13
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be screened and recruited from adult patients either scheduled for elective 2D-echo at a cardiology clinic at the Prince of Wales Hospital, or attending the emergency department at the Prince of Wales Hospital.

Brief summary: Objective:

The Ultrasonic Cardiac Output Monitor (USCOM) is a non-invasive, quantitative method for measuring and monitoring cardiovascular haemodynamic parameters in patients. The aims of this study are:

1. To investigate whether USCOM-derived haemodynamic parameters such as Cardiac output (CO), inotropy and oxygen delivery (DO2) have a role in the diagnosis of patients with a compensated heart failure syndrome (cHFS) or acute decompensated heart failure syndrome (adHFS)
2. To investigate whether USCOM-derived haemodynamic parameters such as CO, inotropy and DO2 correlate with heart failure staging, especially New York Heart Association (NYHA) class and American Heart Association (AHA) stage.
3. To investigate whether USCOM-derived haemodynamic parameters such as velocity time interval (vti), stroke volume (SV), CO, SV index (SVI), CO index (CI), inotropy and DO2 correlate with ejection fraction.
4. To investigate whether USCOM-derived haemodynamic variables may be used as prognostic indicators of 30-day, 6-month and 1-year Major Adverse Cardiac Events (MACE).
5. To evaluate the agreement between hemodynamic measurements obtained using the Ultrasonic Cardiac Output Monitor (USCOM®; USCOM Ltd., Sydney, Australia), and reference standards as determined by 2 Dimensional echocardiography (2D-echo) measurements in groups of haemodynamically stable and unstable adult patients.

Design:

This prospective observational cohort study will be conducted in the Prince of Wales Hospital in Hong Kong.

Setting and Subjects:

Patients will be screened and recruited from adult patients either scheduled for elective 2D-echo at a cardiology clinic at the Prince of Wales Hospital, or attending the emergency department at the Prince of Wales Hospital.

Interventions:

Haemodynamic measurements made using the USCOM and 2D-echo will be compared. In order to assess inter-observer variability, a second, blinded operator will repeated 15% of scans.

Detailed description: Acute heart failure syndromes (aHFS) cause almost 1 million hospitalizations annually in the United States and are the leading cause of hospitalization in persons aged over 65 years. In 2003, inpatient management of aHFS cost an estimated $12.7 billion in the United States. In 2003, 12.5% of the population in Hong Kong were aged over 65, the third highest proportion of elderly among all countries, and it is postulated that by 2033, the proportion of the elderly in the population will increase to 25%. With the growing elderly population, and the increasing prevalence of hypertension and ischemic heart disease (the major causes of heart failure), heart failure has become a major health care issue globally. In western countries the incidence ranges from 1 to 10 cases/1000/year. Other studies suggest that heart failure is a large and growing public health burden throughout Europe.

Acute exacerbation of heart failure symptoms is a common emergency department (ED) presentation and is known as acute decompensated heart failure (adHF). Acute decompensated heart failure represents the single greatest cost to the US hospitals funded by Medicaid. In Hong Kong (HK), the incidence rate of heart failure was 3-3.8/1000/year rising to 20/1000/year in women over the age of 85 years in recent years. It has been estimated that 7% of all acute medical admissions was due to this condition. In recent years there has been a 10% annual increase in admissions for patients with adHF. Currently in Hong Kong, the vast majority of ED patients with adHF are admitted as inpatients to hospital. In 2005, an audit of outcomes in patients with acute cardiogenic pulmonary oedema, the most severe manifestation of heart failure, presenting to the emergency department at the Prince of Wales Hospital showed that nearly 30% of patients die within 30 days, and a further 30% require readmission within 30 days. Recent evidence from the USA suggests that ED operated observation units are effective in managing low to medium risk adHF patients, reducing length of stay (LOS) for these patients without adversely affecting readmission rate, morbidity and mortality.

2 Dimensional echocardiography (2D-echo) is a conventional standard-of-care tool for non-invasive hemodynamic assessments in adults. In stable settings, heart failure is often characterized and classified according to ejection fraction measured by echocardiography which may be considered a pragmatic gold standard. However, the use of 2D-echo requires highly trained personnel. Obtaining measurements and calculating fundamental cardiovascular parameters such as cardiac output (CO)may take anywhere between 30 to 45 minutes, which is impractical for any setting, let alone an acute care setting. Further, such personnel are frequently not available in emergency departments. The feasibility of real time haemodynamic assessments is therefore limited with 2D-echo. More sophisticated echocardiographic techniques have been developed in an attempt to overcome the problems of sensitivity to preload and particularly afterload, but have achieved little penetration in critical care.

In acute critical care settings, the diagnosis of adHF is based on the history and clinical signs, sometimes aided by echocardiography, chest radiography and blood markers such as B-type Natriuretic Peptide (BNP). The value of BNP over clinical assessment in patients presenting with dyspnoea has been questioned and there is a need for other tools to improve diagnosis. Commencement, dosing, and withdrawal of vasopressors, vasodilators, and inotropes is still largely based on clinical assessment, sometimes assisted by measurement of surrogates of inotropy such as ejection fraction (EF) or aortic ejection velocity, despite the well-known shortcomings of these indices in critical care. This is particularly so in complex surgical patients where vascular tone and fluid loading status are highly variable and changing.

Heart failure is an abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues, despite normal filling pressures (or only at the expense of increased filling pressures). The commonest causes are hypertension or ischemic heart disease. If this definition holds, then heart failure should be associated with some measure of reduction in inotropy or oxygen delivery. Until recently there was no simple non-invasive, bedside test that could aid the assessment of patients with heart failure. Whilst inotropy (or myocardial contractility) as a concept is well known to all clinicians, it is seldom thought of as a measurable quantity.

USCOM has been introduced as a non-invasive bedside haemodynamic monitoring tool that utilizes continuous-wave Doppler ultrasound. The USCOM has a number of advantages. It accuracy, validity and reasonable precision has been confirmed by many studies and in a variety of contexts. It is easily portable, takes only several minutes to obtain reliable measurements in most cases, and can be conducted by trained physicians or nurses.

Some studies have shown good agreement between USCOM and echocardiography but others have been less convincing. With this in mind, there is still a need for further studies to confirm or refute levels of agreement between USCOM and echocardiography.

The potential utility of USCOM for assessing patients with adHF has recently been suggested. Inotropy measurements derived from USCOM are greatly reduced in patients with New York Heart Association (NYHA) Class IV and American Heart association (AHA) stage C, acute left ventricular failure, when compared with healthy controls. These findings have led to the proposal that as USCOM can measure inotropy, then it could be used to assess and to manage heart failure. Although inotropy, derived by USCOM, is low in patients with adHF and NYHA class IV, nevertheless there is no evidence of a dose-relationship between USCOM-derived inotropy and NYHA class, or of a correlation with increasing severity of adHF, with ejection fraction.

Many, if not most, emergency departments throughout the world do not have 2D-echo available 24 hours a day, if at all. The value of BNP testing to improve outcomes has been questioned but even if used, it is frequently not available in many hospitals. As such the assessment and diagnosis of heart failure, and the means to monitor the effect of therapy, constitutes a major unmet need in clinical practice and especially in emergency departments.

Aim

The overall aim of this study is to investigate whether USCOM-derived haemodynamic parameters may have diagnostic, risk-stratification, prognostic and therapeutic monitoring potential in patients with suspected heart failure. The specific objectives are:

1. To investigate whether USCOM-derived haemodynamic parameters such as CO, inotropy and oxygen delivery (DO2) have a role in the diagnosis of patients with a compensated heart failure syndrome (cHFS) or acute decompensated heart failure syndrome (adHFS)
2. To investigate whether USCOM-derived haemodynamic parameters such as CO, inotropy and DO2 correlate with heart failure staging, especially NYHA class and AHA stage.
3. To investigate whether USCOM-derived haemodynamic parameters such as velocity time interval (vti), stroke volume (SV), CO, SV index (SVI), CO index (CI), inotropy and DO2 correlate with ejection fraction.
4. To investigate whether USCOM-derived haemodynamic variables may be used as prognostic indicators of 30-day, 6-month and 1-year Major Adverse Cardiac Events (MACE).
5. To evaluate the agreement between hemodynamic measurements obtained using the Ultrasonic Cardiac Output Monitor (USCOM®; USCOM Ltd., Sydney, Australia), and reference standards as determined by 2D-echo measurements in groups of haemodynamically stable and unstable adult patients.

Data collection and measurable parameters

* Demographics including sex, age, height and weight
* Chief complaints, concurrent illnesses and significant past history
* Clinical signs including respiration rate, heart rate, systolic blood pressure, diastolic blood pressure, oxygen saturation and CGS.
* USCOM derived haemodynamic parameters
* Full blood examination, urea and electrolytes, arterial or venous blood gases, blood glucose, lactate, BNP, ECG and chest x-ray
* ED diagnosis, disposition from ED, hospital length of stay, ICU length of stay, hospital diagnosis and in-hospital mortality All the above data will be entered into a database that is securely stored with access only by the investigators.

Definition of haemodynamic parameters:

* Flow time corrected (FTc) is calculated using Bazett's formula: FTc = FT/√tHR, where tHR = the heart beat period in seconds (s). The unit of FTc is ms.
* Velocity time integral (vti) is the integral of the flow profile, i.e. the distance the blood travels in one beat. The unit of vti is m/s.
* Cardiac output (CO) is the volume of blood pumped by the heart in one minute: CO = SV x HR. The unit is l/min.
* Cardiac index (CI) is equal to CO divided by BSA. The unit is l/min/m2.
* Inotropy index refers to (Potential energy + Kinetic energy) divided by body surface area. The unit of inotropy is W/m2.
* Minute distance (MD) is the distance a blood cell travels in metres per minute (m/min). MD = HR x vti, where vti = velocity time integral or stroke distance, which is the distance in centimetres (cm) a single reflector travels per cycle, and is defined as the area of the flow.
* Stroke volume (SV) is the volume of blood ejected from the heart during one systolic stroke. SV = vti x πr2,where πr2 = flow cross sectional area. The unit of SV is ml.
* Stroke volume index (SVI) is SV divided by BSA and the unit is ml/m2.
* Stroke volume variation (SVV) is the percentage change in SV between a group of beats. SVV = (SVmax - SVmin x 100) / \[(SVmax + SVmin)/2\].
* Systemic vascular resistance (SVR) is the pressure against which the heart pumps. SVR = MAP/CO. The unit is d.s.cm-5.
* Systemic vascular resistance index (SVRI) SVRI = SVR x BSA d.s.cm-5m2.
* Oxygen delivery (DO2) is calculated by the equation: DO2 = 1.34 x Hb x SpO2/100 x CO, where Hb = hemoglobin in grams of hemoglobin per litre of blood (g/l); SpO2 = the peripheral oxygen saturation as a percentage (%). The unit of DO2 is ml/min.
* Oxygen delivery index (DO2I) is equal to DO2 divided by BSA. The unit of DO2I is ml/min/m2.
* Inotropy index refers to (Potential energy + Kinetic energy) divided by body surface area. The unit of inotropy is W/m2.

This project will provide essential data on the potential for clinicians without access to echocardiography but with access to USCOM, to effectively and safely assess patients with cHF, and adHF. Confirming the value of USCOM will enable the earlier diagnosis of heart failure and cardiogenic shock, earlier appropriate management, will remove the guesswork and uncertainty as whether or not to administer diuretics, intravenous fluid, vasodilators, vasoconstrictors, inotropes, chronotropes or blockers. This will open the door for trials orientated to optimizing haemodynamics in the cold and acute critical care settings, thus permitting optimal use of life-saving therapies, and optimizing survival. Such early treatment options should reduce the need for admission to hospital and length of hospital stay.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years, AND
2. Written informed consent by patient or nearest relative where appropriate, AND Either
3. Referred for echocardiography, OR
4. At least one typical symptom and one typical sign consistent with possible heart failure, OR
5. Healthy volunteers

Exclusion Criteria:

* Age \<18 years
* Prior enrollment in study
* Patients with known or suspected pregnancy

Primary outcomes:
measure: Difference in mean (SD) inotropy between New York Heart Association (NYHA) stages I, II, III and IV
timeFrame: On Day 1
Secondary outcomes:
measure: Difference in mean (SD) vti, FTc, SV, SVI, CO, CI, MD, SVR, SVRI, SVV, DO2, DO2I, Inotropy and ejection fraction
timeFrame: On Day 1
measure: Difference in mean (SD) vti, FTc, SV, SVI, CO, CI, MD, SVR, SVRI, SVV, DO2, DO2I, Inotropy and AHA stage
timeFrame: On Day 1
measure: Agreement between CO and SV measured separately by USCOM and 2D-Echo
timeFrame: On Day 1
measure: Number of subjects with and without Major Adverse Cardiac Events (MACE).
timeFrame: 30-days, 6-months and 1-year
measure: Number of subjects with and without acute decompensated heart failure syndrome (adHFS)
timeFrame: On Day 1
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Prince of Wales Hospital
Study officials:
affiliation: Accident & Emergency Medicine Academic Unit
name: Timothy H Rainer, MD FCEM
role: PRINCIPAL_INVESTIGATOR
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