Clinical trial NCT03437148: Non-Invasive Shunt Quantification in Interatrial Communication
Official title: Shunt Quantification in Atrial Septal Defect Using Inert Gas Rebreathing and Thoracic Bioimpedance: Comparison With the Gold Standard Method
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Congenital Heart Diseases
Hemodynamic
Cardiac Output
Keywords: Pulmonary to systemic blood flow
Non-invasive measurement
Inert gas rebreathing
Bioimpedance cardiograph
Atrial Septal Defect
Congenital heart disease
Cardiac Output
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Sport Medicine Department, CHU Clermont-Ferrand
name: Cardiology and Vascular Department, CHU Clermont-Ferrand
First posted: 2018-02-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Shunt quantification in atrial septal defect (ASD) is estimated by Echocardiography-Doppler, with the pulmonary-to-systemic blood flow ratio: Qp/Qs. Higher is the ratio, more important is the shunt, and the consequence on right ventricular function. A value higher than 1.5 is one of the criteria for percutaneous closure of Secundum ASD. Maatouk and al. have demonstrated that a shunt fraction (Qp/Qs) over 3 is a predictive factor of an incomplete reversibility of the right ventricular remodeling \[1\]. Even if the accuracy of Doppler echocardiography is admitted for Qp/Qs measurement, there is still some technical difficulties. Thus, the right cardiac catheterization for O2 consumption measurement by the direct Fick method is used. The major inconvenient is the potential risk of adverse effects. Non-invasive methods have been developed using physical properties (as the thoracic bioimpedance) or inert gas rebreathing technique. Thoracic Bioimpedance (TB) and inert gas rebreathing (IGR) techniques have been studies on healthy individual and different respiratory or cardiac diseases to evaluate the cardiac output (CO). TB and IGR measure the systemic and pulmonary blood flow respectively. Without shunt the pulmonary blood flow is equal to the systemic blood flow.

Thus, Investigator suppose that combine the two techniques in disease with shunt, will allow a quantification of the shunt fraction Qp/Qs as accurate as with the gold standard technique (Fick method and Echocardiography Doppler).

The purpose of the study is to evaluate the feasibility and the accuracy of the non-invasive measurement of the Qp/Qs ratio in secundum ASD using the IGR technique and the TB versus the two gold standard techniques: the Fick method and the Echocardiography-Doppler.

The study hypothesizes that the values of Qp et Qs determined by IGR et TB respectively are in the same range of values that the one determined by gold standard techniques.

Detailed description: Shunt quantification and their hemodynamic consequences have a major importance in the evaluation of heart diseases. Atrial septal defect (ASD) has an intracardiac left-to right shunt, leading to an over pulmonary output with ventricular and pulmonary effects. Measurements of the LTR in ASD requires the determination of the pulmonary blood flow (Qp) and the systemic blood flow (Qs).

Two gold standard techniques are usually used to measure the pulmonary to systemic blood flow ratio (Qp/Qs): either invasive by performing a right heart catheterization, with the direct Fick method, or non-invasive by using the Echocardiography-Doppler (ED) First determine by ED by the successively measure of the Qp at the pulmonary annular and the Qs at the aortic annular, this technique is largely available, reproducible and accurate.

However, some limits are pointed with this non-invasive gold standard method: underestimation of shunt quantification in case of large septal defect, the accuracy depends on the operator experience, the lack of precision to measure pulmonary annular area especially on adults leading to a wrong measure of the pulmonary blood flow.

In case of doubt about pulmonary hypertension or difficulties in hemodynamic evaluation, the cardiologists perform a right heart catheterization to measure the CO by the Fick method .

Concerning the other non-invasive approach, thoracic bioimpedance (TB) have been developed in the middle of the twenty-one centuries by Kubiceck to measure cardiovascular parameters in astronauts has been largely study. Moreover, hemodynamic parameters are not stable but varies continuously according to the "hemodynamic state".

High of interest in the field of the non-invasive hemodynamic device, Inert gas rebreathing (IGR) measures the pulmonary blood flow, at rest and on exercise in healthy patient and different cardiorespiratory diseases. The Innocor® (Innovision, Odense, Denmark) uses a rebreathing bag containing a mixing of N2O (0,5%) SF6 (0,1%) and O2 (28%) diluted with atmospheric air. At the steady state of the insoluble inert gas, sulphur hexafluoride SF6, the wash out rate of N2O during rebreathing is calculated, which is proportional to the Qp. Many studies on healthy people confirms its accuracy, safety, reproducibility to measure CO . Agostoni et al. assess the Innocor® on patients with stable heart failure at rest and exercise comparatively to Thermodilution (ThD) and Fick method . They found a good correlation between the three methods at exercise. They found a tendency on underestimation of the IGR technique for CO measurement in comparison to Fick method . Few studies are available on the IGR technique use in CHD population. Tested on a paediatric population, investigators have proved its feasibility on exercise.Secondary they focused on ASD paediatric population. The CO were measured at exercise before and after percutaneous or surgical closured. They confirm the reproducibility, and feasibility of the IGR . Investigators found a similar agreement with the Fick method for patients with CHD without shunting or with right-to-left shunt .

To our knowledge, no study has focused on the concomitant used of two non-invasive technique to measure the shunt fraction in diseases with shunt. Some have suggested the interest of such a method in chronic obstructive pulmonary disease (COPD) .In fact, CO measured at rest and exercise shows a statistical difference between the IGR and TB due to the shunt effect and right-to-left shunt in COPD. Thus, the IGR and TB determine a pulmonary cardiac output (Qp) and a systemic cardiac output (Qs) respectively.

Based on these results, Investigator hypothesis that the combined used of the IGR and TB will enhance the precision and accuracy of the shunt fraction measurement.

The aim of this study is to validate the double non-invasive pulmonary-to-systemic ratio measurements on ostium secundum ASD in comparison to the two-gold standard method: the direct Fick method and the Echocardiography-Doppler.

Eligibility criteria: Inclusion Criteria:

* cooperate patients over 18 years, having a OS ASD with an indication of interventional closure according to the European Cardiology society guidelines of 2010.
* Patients with significant shunt (signs of right ventricular volume overload) and Pulmonary Vascular Resistance (PVR) \<5WU
* ASD, regardless the size, with suspicion of paradoxal embolism
* Patients with PVR \> or egal 5 WU but \<2/3 Systemic Vascular Resistance or Pulmonary Arterial Pressure \< 2/3 systemic pressure and evidence of net Left-to Right shunt (Qp/Qs \> 1,5)
* with the French Social Security System

Exclusion Criteria:

* Pregnant women and breastfeeding women
* Difficulties of cooperation (patient under assisted ventilation)
* Chronic Obstructive Pulmonary disease or respiratory failure
* Complex congenital heart disease
* Antiplatelet contraindication
* Patients under protection, vulnerable patients
* No consent
* Contraindication of the non-invasive devices
* Physioflow (Manatec, France): patients with pacemaker, with a cardiorespiratory support and assistance, severe aortic insufficiency
* Innocor (Innovision, Odense, Denmark): to our knowledge, and according to the user instructions, there is no contraindication

Primary outcomes:
measure: shunt fraction
timeFrame: at 1 hour
Secondary outcomes:
measure: shunt fraction Qp/Qs after closure
timeFrame: at 1 hour
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Ruddy RICHARD
role: PRINCIPAL_INVESTIGATOR
References:
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