Tetralogy of Fallot for Life
- Conditions
- Congenital Heart DiseaseTetralogy of FallotCongenital Heart Defect
- Registration Number
- NCT02968264
- Lead Sponsor
- Population Health Research Institute
- Brief Summary
The aim is to conduct a prospective multi-centre international inception cohort study with an enrollment goal of 3,000 TOF patients and 2 year follow-up post-repair. The proposed sample size and methodology will result in statistically powerful results to allow for evidence-based change to current TOF surgical practices.
- Detailed Description
Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart defect consisting of 7-10% of all congenital heart disease with an estimated annual global incidence rate of 38,000. It is fatal if untreated; only 50% of patients are alive at 1 year of age. Surgery has dramatically improved the survival so that \>95% of repaired TOF children are alive by one year. The initial justified enthusiasm for the benefit of surgical therapy are now tempered by the findings of late sudden cardiac death secondary to right ventricular (RV) dysfunction. The original trans-ventricular/trans-annular patching repair results in significant pulmonary insufficiency which leads to RV dilation, subsequent functional tricuspid regurgitation, atrial arrhythmias, and eventual RV failure and ventricular arrhythmias. In attempt to break this cycle, an increasing number of patients are undergoing late pulmonary valve implantation.
Recognizing that the RV adapts to stress signals has led to the idea that leaving mixed residual stenosis and regurgitation may yield to an adaptive change that limits RV dilation while still allowing for adequate cardiac output. Early attempts to limit pulmonary insufficiency and RV damage involve minimal trans-annular patching or complete annulus preservation (AP). Emerging data suggest that patients with a mixed lesion have improved survival, so that 96.6% are alive at 25-years in comparison to 85-90% survival for the conventional technique.
Preliminary Data: A review of data comparing AP to TAP repair at our institution (n=185, AP repair=124, TAP=61) demonstrated that at 10-15 year follow-up those who received an AP repair had smaller RV volumes and pulmonary regurgitant jet width. They were also seen to have improved exercise capacity as measure by VO2 max tests. The AP technique also has been seen to significantly decrease the risk of reoperation in comparison to TAP, 11% and 29% respectively.
Current Problem: Although trans-ventricular VSD closure along with a TAP is known to result in increased risk of long-term morbidity and mortality, it continues to be the predominant repair strategy implemented globally according to STS/EACTS databases. Reasons for this are:
* Trans-ventricular/TAP approach is technically easier than annulus preservation, which often requires multiple pump runs
* There is a fear of leaving too much obstruction
* High quality evidence supporting one approach over the other is lacking.
Gaps in Literature
1. Most data on the impact of surgical strategy emerge from single centre experiences that are retrospective and based on small patient population. This makes the results difficult to standardize to the general TOF population.
2. Retrospective registry data published by STS and EACTS omit many crucial surgical and clinical variables that can potentially impact outcomes.
3. None of the current evidence are based on anatomically matched/adjusted patients
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1108
- TOF with RVOT stenosis. TOF is defined as anterio-cephalad deviation of the ventricular outlet septum with no more than 50% aortic override and a single outflow VSD.
- TOF with pulmonary atresia and confluent pulmonary arteries.
- Admitted with intent to treat (i.e. patient planned to undergo a primary or staged repair).
- Patients with coronary artery anomalies, right aortic arch, and 22q11 deletion may be included
- TOF with absent pulmonary valve
- Other major cardiac anomalies such as AVSD, multiple VSDs, right atrial isomerism, and MAPCAs. In this instance, the definition of MAPCAs does not include dilated bronchial collateral arteries.
- Unbalanced ventricles precluding biventricular repair
- Major genetic abnormalities/syndromes e.g. trisomy 13,18, and 21
- Major extra cardiac anomalies e.g. diaphragmatic hernia, omphalocele, absent sternum, cerebral palsy
- Infective endocarditis as an indication for intra-cardiac repair
- Stroke in the last 30 days prior to palliation or intra-cardiac repair
- Known diagnosis of HIV or hepatitis B
- Any previous cardiac procedures
- Patient's circumstance that precludes completion of follow-up telephone call and/or obtaining information from the 2-year cardiology follow-up
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method RV physiology and morphology 2 years post-repair To determine the association between baseline morphology, surgical repair technique (various surgical strategies for VSD closure and managing the RVOT), and RV physiology and morphology at 2 years obtained from echocardiogram studies.
- Secondary Outcome Measures
Name Time Method Number of patients undergoing various palliation procedures and surgical repair strategies 2 years To determine the pattern of palliation procedures (BT shunt, RVOT stent, or balloon dilation), surgical repair strategy (staged versus primary repair), and surgical repair technique (AP, minimal TAP, standard TAP) at participating centres.
Cardiovascular mortality rate 30 days and 2 years after repair To determine the 30-day and 2 year cardiovascular mortality rate (for equivalent patients) after primary and staged repair.
Rate of palliation failure 2 years To determine the rate of palliation failure following various palliation techniques
Effect of palliation procedures on cardiac morphology 2 years To determine the possible effect of palliative procedures (BT shunts, balloon dilation, stent insertion) on cardiac morphology (growth of the infundibular chamber, the pulmonary annulus and PA branches' diameter) and subsequent repair technique.
Post-operative restrictive physiology 2 years To determine the relationship between repair technique/strategy and prevalence of postoperative restrictive physiology as defined by the presence of antegrade flow in pulmonary artery during atrial contraction on echocardiogram.
Cardiac re-interventions 2 years To determine the relationship between TOF repair strategy/technique on the incidence and prevalence of cardiac re-interventions (e.g. pulmonary valve implantation, RVOT stent insertion or balloon dilatation)
RV physiology and morphology following TOF pulmonary atresia repair 2 years To determine the right ventricular morphological and physiological adaptations to severe pulmonary stenosis or regurgitation using repaired TOF pulmonary atresia as a model. For example RV/LV end diastolic and systolic diameter ratio. RV and LV wall thickness relation to outflow gradient obtained by echocardiogram studies.
Trial Locations
- Locations (20)
Children's Cardiac Center - Ukraine
🇺🇦Kyiv, Ukraine
Manmohan Cardiothoracic Vascular and Transplant Center
🇳🇵Kathmandu, Nepal
King Abdulaziz University Hospital
🇸🇦Jeddah, Makkah, Saudi Arabia
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Morgan Stanley Children's Hospital
🇺🇸New York, New York, United States
Okayama University Hospital
🇯🇵Okayama, Japan
Guangzhou Women and Children's Medical Center
🇨🇳Guangdong, China
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institutev
🇮🇳Mumbai, India
Fortis Escorts Heart Institute
🇮🇳New Delhi, Delhi, India
West China Hospital
🇨🇳Chengdu, Sichuan, China
Shanghai Xinhua Hospital
🇨🇳Shanghai, China
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
National Cardiovascular Center Harapan Kita
🇮🇩Jakarta, Indonesia
Academician E.N. Meshalkin Research
🇷🇺Novosibirsk, Russian Federation
King Faisal Specialist Hospital and Research Centre - Jeddah
🇸🇦Jeddah, Saudi Arabia
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Beijing Fuwai Hospital
🇨🇳Beijing, China
Shanghai Children's Medical Centre
🇨🇳Shanghai, China
Guangdong Cardiovascular Institute
🇨🇳Guangdong, China