integrated computational modeling of right heart mechanics and blood flow dynamics in congenital heart disease

Conditions: Congenital Heart Disease; Pulmonary Hypertension

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.

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.

Eligibility criteria:
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)