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

NCT03217240 | Unknown

• 1 other identifier: NHeartCentreS
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Congenital Heart Disease; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Develop a comprehensive (BME) RnD platform for in-depth study of RV mechanics, blood flow and function in Congenital Heart Disease

  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

Study Arms (2)

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; Other: Cardiopulmonary Exercise Test; Other: Blood Sampling for all participants

Healthy Volunteer

Cardiac Magnetic Resonance - MRI Cardiopulmonary Exercise Test Blood Sampling for all participants

Procedure: Cardiac Magnetic Resonance - MRI; Other: Cardiopulmonary Exercise Test; Other: Blood Sampling for all participants

Interventions

Cardiac Magnetic Resonance - MRI PROCEDURE

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.

Congenital Heart Disease; Healthy Volunteer

Cardiopulmonary Exercise Test OTHER

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.

Congenital Heart Disease; Healthy Volunteer

Blood Sampling for all participants OTHER

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

Congenital Heart Disease; Healthy Volunteer

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• For patients with repaired tetralogy of Fallot
• Survivors of TOF repair more than one year after repair
• Aged: 12-80
• For patients with pulmonary hypertension
• Signed informed consent prior to initiation of any study mandated procedure
• Age between 12 - 80 years
• 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
• Aged :12-80
• Asymptomatic and ambulant
• Resting blood pressure \<140/90 mmHg

You may not qualify if:

• Non-cardiac illness with a life expectancy of less than 2 years
• Previous heart, kidney, liver or lung transplantation
• Contraindication to MRI examination
• Cardiac pacemaker
• Brain aneurysm or clips
• Electronic implants or prosthesis
• Eye metal foreign body injury
• Severe claustrophobia
• Severe renal impairment, glomerular filtration rate \<30ml/min/1.73m2
• Pregnancy
• 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)
• Concurrently taking any medications for cardiovascular disease (including hypertension)
• 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)

Sponsors & Collaborators

• National Heart Centre Singapore: lead
• Ministry of Health, Singapore: collaborator

Study Sites (3)

National University Hospital

Singapore, 119074, Singapore

NOT YET RECRUITING

National Heart Centre

Singapore, 169609, Singapore

RECRUITING

KK Women's and Children's Hospital

Singapore, 229899, Singapore

NOT YET RECRUITING

Related Publications (15)

• Douglas PS, Pontone G, Hlatky MA, Patel MR, Norgaard BL, Byrne RA, Curzen N, Purcell I, Gutberlet M, Rioufol G, Hink U, Schuchlenz HW, Feuchtner G, Gilard M, Andreini D, Jensen JM, Hadamitzky M, Chiswell K, Cyr D, Wilk A, Wang F, Rogers C, De Bruyne B; PLATFORM Investigators. Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study. Eur Heart J. 2015 Dec 14;36(47):3359-67. doi: 10.1093/eurheartj/ehv444. Epub 2015 Sep 1.

  PMID: 26330417 BACKGROUND

• Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, Erglis A, Lin FY, Dunning AM, Apruzzese P, Budoff MJ, Cole JH, Jaffer FA, Leon MB, Malpeso J, Mancini GB, Park SJ, Schwartz RS, Shaw LJ, Mauri L. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012 Sep 26;308(12):1237-45. doi: 10.1001/2012.jama.11274.

  PMID: 22922562 BACKGROUND

• Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, Dunning A, DeFrance T, Lansky A, Leipsic J, Min JK. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol. 2011 Nov 1;58(19):1989-97. doi: 10.1016/j.jacc.2011.06.066.

  PMID: 22032711 BACKGROUND

• Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Lung B, Lancellotti P, Pierard L, Price S, Schafers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M; ESC Committee for Practice Guidelines (CPG); Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg. 2012 Oct;42(4):S1-44. doi: 10.1093/ejcts/ezs455. Epub 2012 Aug 25. No abstract available.

  PMID: 22922698 BACKGROUND

• Egidy Assenza G, Cassater D, Landzberg M, Geva T, Schreier J, Graham D, Volpe M, Barker N, Economy K, Valente AM. The effects of pregnancy on right ventricular remodeling in women with repaired tetralogy of Fallot. Int J Cardiol. 2013 Oct 3;168(3):1847-52. doi: 10.1016/j.ijcard.2012.12.071. Epub 2013 Jan 28.

  PMID: 23369674 BACKGROUND

• Geva T, Sandweiss BM, Gauvreau K, Lock JE, Powell AJ. Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging. J Am Coll Cardiol. 2004 Mar 17;43(6):1068-74. doi: 10.1016/j.jacc.2003.10.045.

  PMID: 15028368 BACKGROUND

• Warnes CA. Adult congenital heart disease importance of the right ventricle. J Am Coll Cardiol. 2009 Nov 17;54(21):1903-10. doi: 10.1016/j.jacc.2009.06.048.

  PMID: 19909869 BACKGROUND

• Kilner PJ, Geva T, Kaemmerer H, Trindade PT, Schwitter J, Webb GD. Recommendations for cardiovascular magnetic resonance in adults with congenital heart disease from the respective working groups of the European Society of Cardiology. Eur Heart J. 2010 Apr;31(7):794-805. doi: 10.1093/eurheartj/ehp586. Epub 2010 Jan 11.

  PMID: 20067914 BACKGROUND

• Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med. 2007 Nov 29;357(22):2277-84. doi: 10.1056/NEJMra072149. No abstract available.

  PMID: 18046031 BACKGROUND

• Zhao X, Lee PT, Hu L, Tan RS, Chai P, Yeo TJ, Leng S, Ouyang R, Bryant JA, Teo LLS, van der Geest RJ, Yip JW, Tan JL, Zhong Y, Zhong L. Right Ventricular Restrictive Physiology Is Associated With Right Ventricular Direct Flow From 4D Flow CMR. JACC Asia. 2024 Oct 22;4(12):912-924. doi: 10.1016/j.jacasi.2024.08.019. eCollection 2024 Dec.

  PMID: 39802994 DERIVED

• Zhao X, Tan RS, Garg P, Chai P, Leng S, Bryant JA, Teo LLS, Yeo TJ, Fortier MV, Low TT, Ong CC, Zhang S, Van der Geest RJ, Allen JC, Tan TH, Yip JW, Tan JL, Hughes M, Plein S, Westenberg JJM, Zhong L. Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects. J Cardiovasc Magn Reson. 2023 Sep 18;25(1):50. doi: 10.1186/s12968-023-00960-x.

  PMID: 37718441 DERIVED

• Zhao X, Garg P, Assadi H, Tan RS, Chai P, Yeo TJ, Matthews G, Mehmood Z, Leng S, Bryant JA, Teo LLS, Ong CC, Yip JW, Tan JL, van der Geest RJ, Zhong L. Aortic flow is associated with aging and exercise capacity. Eur Heart J Open. 2023 Aug 26;3(4):oead079. doi: 10.1093/ehjopen/oead079. eCollection 2023 Jul.

  PMID: 37635784 DERIVED

• Zhao X, Leng S, Tan RS, Chai P, Yeo TJ, Bryant JA, Teo LLS, Fortier MV, Ruan W, Low TT, Ong CC, Zhang S, van der Geest RJ, Allen JC, Hughes M, Garg P, Tan TH, Yip JW, Tan JL, Zhong L. Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension. J Cardiovasc Magn Reson. 2022 Dec 1;24(1):61. doi: 10.1186/s12968-022-00896-8.

  PMID: 36451198 DERIVED

• Zhao X, Hu L, Leng S, Tan RS, Chai P, Bryant JA, Teo LLS, Fortier MV, Yeo TJ, Ouyang RZ, Allen JC, Hughes M, Garg P, Zhang S, van der Geest RJ, Yip JW, Tan TH, Tan JL, Zhong Y, Zhong L. Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2022 Jan 3;24(1):4. doi: 10.1186/s12968-021-00832-2.

  PMID: 34980199 DERIVED

• Leng S, Tan RS, Guo J, Chai P, Zhang G, Teo L, Ruan W, Yeo TJ, Zhao X, Allen JC, Tan JL, Yip JW, Chen Y, Zhong L. Cardiovascular magnetic resonance-assessed fast global longitudinal strain parameters add diagnostic and prognostic insights in right ventricular volume and pressure loading disease conditions. J Cardiovasc Magn Reson. 2021 Apr 1;23(1):38. doi: 10.1186/s12968-021-00724-5.

  PMID: 33789701 DERIVED

Related Links

• Clinical outcomes of fractional flow reserve.
• Diagnostic accuracy of fractional flow reserve from anatomic CT angiography
• Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms.
• Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
• The effects of pregnancy on right ventricular remodeling in women with repaired tetralogy of Fallot
• Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging
• Adult congenital heart disease importance of the right ventricle
• Recommendations for cardiovascular magnetic resonance in adults with congenital heart disease from the respective working groups of the European Society of Cardiology
• Computed tomography--an increasing source of radiation exposure

Biospecimen

Retention: SAMPLES WITHOUT DNA

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

MeSH Terms

Conditions

Heart Defects, Congenital; Hypertension, Pulmonary

Interventions

Exercise Test; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative

Study Officials

• Dr Zhong Liang

  Researcher

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhong Liang

CONTACT

67042237; zhong.liang@nhcs.com.sg

Nurkhairunisah Abdul Rahim

CONTACT

67042263; nurkhairunisah.abdul.rahim@nhcs.com.sg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 14, 2017
• Study Start: June 5, 2017
• Primary Completion: January 1, 2019
• Study Completion: August 30, 2019
• Last Updated: July 14, 2017

Record last verified: 2017-07

Locations

SG (3)