What is the Single Ventricle Reconstruction (SVR) trial?

The Single Ventricle Reconstruction Trial

The Single Ventricle Reconstruction (SVR) Trial was the first randomized clinical trial of surgical approaches for congenital heart disease, comparing two shunt types during the Norwood procedure for infants with hypoplastic left heart syndrome (HLHS) and other single right ventricle anomalies. 1

Background and Purpose

• The SVR trial randomized infants with HLHS and other single right ventricle anomalies to receive either a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right-ventricle-to-pulmonary-artery shunt (RVPAS) during their Norwood procedure 1, 2
• Single ventricle physiology represents one of the most complex forms of congenital heart disease (CHD), where only one effective pumping chamber exists, requiring reconstructive surgery or heart transplantation 3
• Although single ventricle defects account for only 1.5% of CHD cases, they contribute disproportionately to morbidity and mortality 3

Trial Design and Methodology

• The primary aim of the initial SVR trial was to compare transplant-free survival between the two shunt types 2
• The trial included 549 subjects across multiple centers in North America 2
• Follow-up studies (SVR III) were designed to assess long-term outcomes in early adolescence (10-15 years of age), including cardiac function, neurodevelopment, and transplant-free survival 1
• Cardiac magnetic resonance imaging (CMR) was used as a key assessment tool, with right ventricular ejection fraction (RVEF) as the primary outcome measure 1, 4

Key Findings

• Initial 1-year results showed better transplant-free survival for the RVPAS group compared to the mBTTS group 5
• However, by 3 years post-randomization, this survival advantage was no longer evident (67% for RVPAS vs. 61% for mBTTS; P=0.15) 5
• The hazard ratio for transplant-free survival showed time-dependent effects: favoring RVPAS before 5 months but favoring mBTTS beyond 1 year 5
• RVPAS subjects had lower pre-Fontan right ventricular ejection fraction compared to mBTTS subjects (41.7±5.1% vs. 44.7±6.0%; P=0.007) 5
• RVPAS subjects required more catheter interventions over time, with an increasing hazard ratio compared to mBTTS subjects 5
• Recoarctation of the aorta occurred in 18% of SVR subjects, with a higher risk in those with RVPAS (hazard ratio 2.0 compared to mBTTS) 2

Surgical Stages in Single Ventricle Reconstruction

• Stage I (Norwood procedure): Performed shortly after birth, includes a systemic-to-pulmonary artery shunt (either mBTTS or RVPAS), atrial septectomy, and aortic-to-pulmonary anastomosis 3
• Stage II (Superior cavopulmonary connection): Typically performed at 3-6 months of age, includes either bidirectional Glenn (BDG) or hemi-Fontan (HF) procedures 3, 6
• Stage III (Fontan completion): Usually performed at 2-5 years of age, directs inferior vena cava blood into the lungs to complete the separation of systemic and pulmonary circulations 3

Long-term Outcomes and Complications

• Common complications after single ventricle palliation include protein-losing enteropathy, thromboembolic complications, ventricular dysfunction, and dysrhythmias 3
• Cardiorespiratory responses to exercise after Fontan completion are typically subnormal, with lower VO2max, cardiac output, and heart rate responses 3
• Pre-adolescents who undergo volume-unloading surgery at an earlier age tend to have better aerobic capacity 3
• Diastolic filling abnormalities are common regardless of ventricular morphology 3

Clinical Implications

• The SVR trial demonstrated that early survival advantages of RVPAS did not persist at 3 years, and RVPAS was associated with worse right ventricular function and more interventions over time 5
• The findings highlight the importance of long-term follow-up in congenital heart disease trials, as early outcomes may not predict later results 5
• Ongoing follow-up studies (SVR III) will provide critical information about adolescent outcomes that may further inform surgical decision-making 1

Imaging Considerations

• CMR has emerged as a valuable tool for assessing single ventricle function in this population, with 75% of enrolled SVRIII participants successfully undergoing CMR 4
• Pre-stage II evaluation is crucial to assess pulmonary arterial pressures, pulmonary vascular resistance, and ventricular volumes 2
• Imaging before stage II surgery should evaluate for obstruction in pulmonary arteries/veins, atrial septal defect, ventricular outflow tract, and aortic arch 3