Integrated Computational modelIng of Right Heart Mechanics and Blood Flow Dynamics in Congenital Heart Disease

July 11, 2017 updated by: National Heart Centre Singapore

Integrated Computational modelIing of Right Heart Mechanics and Blood Flow Dynamics in Congenital Heart Disease ("INITIATE")

Advances in paediatric cardiology and cardiac surgery have enabled the survival of most patients born with congenital heart disease (CHD) into adulthood. Many CHD patients have undergone palliative or reparative surgery earlier in life. As patients survive into adulthood, they may need intervention or surgery for residual haemodynamic lesions. This is because they are at risk of arrhythmias secondary to structure heart disease and are susceptible to acquired heart disease. In these patients, pre-operative and post-operative evaluation of right ventricular (RV) structure (shape and volume) and function is an essential component of clinical management.

Advances have been made in cardiac imaging so that accurate assessment of the right heart chamber in terms of its structure, function and physiology is possible. However, this technology has as yet never been applied in an effort to comprehensively assess RV structure, function and physiology. Cardiac Magnetic Resonance (CMR) will be used in this comprehensive assessment of structure and function. Thus, this research will allow development of a comprehensive integrated biomedical engineering (BME) R&D platform for in-depth study and clinical diagnosis of the RV structure-function relationship and physiology and its association with biomarker, and exercise capacity in CHD.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The incidence of Congenital Heart Disease (CHD) in live new-borns is estimated to vary from 4.1/1000 to 12.3/1000. The improvement in survival of CHD patients has led to burgeoning numbers of grown-up CHD.The majority of these CHD patients face a lifetime of problems including RV dilation, ventricular arrhythmias, and sudden cardiac death.Considering inflation to visit costs and added image technology for diagnosis, the cost of each patient is expected to increase .In contrast to adult patients with acquired heart disease, abnormalities of the RV are ubiquitous in children and adults with CHD.

Currently, clinical evaluation includes ECG and pulse oximetry alongside clinical examination. Investigation of RV anatomy and physiology is evolving from a reliance on invasive studies (right heart catheterization or RHC) to non-invasive imaging techniques such as echocardiography, nuclear scintigraphy, computed tomography, and CMR .2D echocardiography is largely operator dependent and suffers from poor inter-study reproducibility.The complex geometry of the RV makes it difficult to accurately quantify remodelling before and after intervention. Nuclear scintigraphy and computed tomography (CT) are constrained by the need for ionizing radiation as well as the poor temporal resolution of the technique.Importantly, existing CMR analytics fail to exploit the full potential of the rich CMR image dataset, and do not yield information on regional RV remodelling, muscle stiffness and blood flow characterization.

Due to the challenges mentioned above, other than RV volumes and ejection fraction, other changes in RV shape and haemodynamics have yet to be considered in the official guidelines used to define eligibility for surgery and to quantify risk of operation. It is plausible that incorporation of additional variables that more comprehensively characterizes fine alterations in RV structure, function and haemodynamics in large risk-stratification models, such as the EuroSCORE and the Society of Thoracic Surgeons' Risk Calculator, may enhance risk stratification and prognostication.

Incorporating novel exploratory RV functional indices (e.g. curvedness, area strain) and computational methods (e.g. CFD, FSI simulations), and then correlating these with clinical and cardiopulmonary exercise test outcomes will allow investigators to have established an unprecedentedly sizeable and rich clinical imaging database that serves both as a touchstone for clinical reference, as well as a repository for future exploratory research.

Investigators tend to develop a comprehensive (BME) Research and Development platform for in-depth study of RV mechanics, blood flow and function in Congenital Heart Disease.

Study Type

Observational

Enrollment (Anticipated)

400

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Singapore
      • Singapore, Singapore, 119074
        • Not yet recruiting
        • National University Hospital
        • Contact:
        • Sub-Investigator:
          • Dr Chai Ping
      • Singapore, Singapore, 229899
        • Not yet recruiting
        • KK Women's and Children's Hospital
        • Contact:
        • Sub-Investigator:
          • Dr Tan Teng Hong
      • Singapore, Singapore, 169609

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

12 years to 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Study will recruit 200 patients and 200 Healthy volunteers from across 3 sites at the following institutions:

  • National Heart Centre
  • National University Hospital

  • KK Women's and Children's Hospital

    200 Congenital Heart Disease Patients 200 Healthy Volunteer

Description

Inclusion Criteria:

For patients with repaired tetralogy of Fallot

  1. Survivors of TOF repair more than one year after repair
  2. Aged: 12-80

For patients with pulmonary hypertension

  1. Signed informed consent prior to initiation of any study mandated procedure
  2. Age between 12 - 80 years
  3. Patient with clinically suspected or known primary PH belonging to one of the following subgroups of the Updated Dana Point Clinical Classification Group 1 (at least 1 of the following a)Idiopathic (IPAH), or b)Heritable (HPAH), or c)Drug or toxin induced, or d)Associated (APAH) with one of the following: i.Connective tissue disease ii.Congenital heart disease

For Healthy volunteers

  1. Aged :12-80
  2. Asymptomatic and ambulant
  3. Resting blood pressure <140/90 mmHg

Exclusion Criteria:

  1. Non-cardiac illness with a life expectancy of less than 2 years
  2. Previous heart, kidney, liver or lung transplantation

  3. Contraindication to MRI examination

    1. Cardiac pacemaker
    2. Brain aneurysm or clips
    3. Electronic implants or prosthesis
    4. Eye metal foreign body injury
    5. Severe claustrophobia
    6. Severe renal impairment, glomerular filtration rate <30ml/min/1.73m2
  4. Pregnancy

Additional exclusion criteria for healthy volunteers:

  1. History of any major medical problems, any cardiovascular disease (such as hypertension or diabetes) or significant renal or lung disease (eg.COPD, Asthma, Pneumonia,Pulmonary embolism,Pulmonary edema,Respiratory tract infection,Bronchiolitis)
  2. Concurrently taking any medications for cardiovascular disease (including hypertension)
  3. Heavy smoking (over 5 sticks per day or who has quit smoking in less than 12 months and had smoked over 5 sticks per day)

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
Congenital Heart Disease
Tetralogy of Fallot Repair/Pulmonary Hypertension Cardiac Magnetic Resonance - MRI Cardiopulmonary Exercise Test Blood Sampling for all participants
Procedure: Cardiac Magnetic Resonance - MRI
All participants will have to undergo CMR which uses interaction of the magnetic properties of body tissues with strong magnetic fields to create images. Participants will be asked to lie on a narrow bed placed inside of a large magnet for about 1 hour. Several sets of images are needed. Participants are required to stay very still and follow the instruction of the MRI technologist who operates the machine from a room next door.
Other: Cardiopulmonary Exercise Test
Participants will be asked to undergo a cardiopulmonary exercise test (CPET). Participants will need to wear a mask. Several electrodes will be placed on the chest to record heart activity during exercise. Participants will need to pedal for at least 8-12 minutes. Pedalling will be instructed to report any symptoms such as chest discomfort, shortness of breath, leg fatigue or dizziness. A small probe will be placed on participant's finger during the test to measure the oxygen content in the blood. Immediately after exercising, participants will rest for 5-10 minutes while the blood pressure and electrocardiogram are monitored. The results will be read by a cardiologist.
Other: Blood Sampling for all participants
Serum samples will be obtained before CMR. The sample will be stored at -80 degree until assay. Investigators will perform various tests related to participants heart function
Healthy Volunteer
Cardiac Magnetic Resonance - MRI Cardiopulmonary Exercise Test Blood Sampling for all participants
Procedure: Cardiac Magnetic Resonance - MRI
All participants will have to undergo CMR which uses interaction of the magnetic properties of body tissues with strong magnetic fields to create images. Participants will be asked to lie on a narrow bed placed inside of a large magnet for about 1 hour. Several sets of images are needed. Participants are required to stay very still and follow the instruction of the MRI technologist who operates the machine from a room next door.
Other: Cardiopulmonary Exercise Test
Participants will be asked to undergo a cardiopulmonary exercise test (CPET). Participants will need to wear a mask. Several electrodes will be placed on the chest to record heart activity during exercise. Participants will need to pedal for at least 8-12 minutes. Pedalling will be instructed to report any symptoms such as chest discomfort, shortness of breath, leg fatigue or dizziness. A small probe will be placed on participant's finger during the test to measure the oxygen content in the blood. Immediately after exercising, participants will rest for 5-10 minutes while the blood pressure and electrocardiogram are monitored. The results will be read by a cardiologist.
Other: Blood Sampling for all participants
Serum samples will be obtained before CMR. The sample will be stored at -80 degree until assay. Investigators will perform various tests related to participants heart function

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Develop a comprehensive (BME) RnD platform for in-depth study of RV mechanics, blood flow and function in Congenital Heart Disease
Time Frame: 3 years
This research will give an in-depth understanding of RV structure-function relationship, mechanics and haemodynamics. This is the foundation for rationale and physiologically-sound clinical decision-making in CHD monitoring and management. In addition, computational modelling of RV blood flow would be the best tool to optimize an individual solution to RV surgery and may ultimately improve surgical planning. This proposal is a pioneering study that can influence the research field and current management in preoperative, intraoperative, and post-operative interventions in CHD patients.
3 years

Collaborators and Investigators

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

Sponsor

National Heart Centre Singapore

Collaborators

Ministry of Health, Singapore

Investigators

  • Principal Investigator: Dr Zhong Liang, Researcher

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

Helpful Links

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)

June 5, 2017

Primary Completion (Anticipated)

January 1, 2019

Study Completion (Anticipated)

August 30, 2019

Study Registration Dates

First Submitted

July 11, 2017

First Submitted That Met QC Criteria

July 11, 2017

First Posted (Actual)

July 14, 2017

Study Record Updates

Last Update Posted (Actual)

July 14, 2017

Last Update Submitted That Met QC Criteria

July 11, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NHeartCentreS

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

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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