In May 2025, in the cardiac surgery operating room of the First Hospital of Jilin University, under the shadowless lamp, 3-year-old girl Ningning lay quietly on the operating table. She was diagnosed with complex congenital heart disease - Tetralogy of Fallot (TOF) at birth. Her young life had been threatened by numerous hypoxic episodes: she needed to squat down to rest after walking a few meters, and her lips turned purple when she cried, as if being choked by an invisible hand. At this moment, the cardiac surgery team was performing a radical operation on her. The operation took only 3.5 hours. Three hours after the operation, Ningning regained consciousness and was weaned off the ventilator. On the third day after the operation, she was discharged home with a smile of recovery.
Ningning's story is not an isolated case but a microcosm of a century of medical progress. Going back to 1944, when Dr. Blalock from Johns Hopkins Hospital in the United States performed the first subclavian artery-pulmonary artery shunt for a TOF child, the simple surgical conditions were alarming - without special instruments, he used tweezers bought from a jewelry store to complete the vascular anastomosis. The moment when 11-month-old baby girl Eileen Saxon's lip color changed from cyanosis to red after the operation marked the beginning of a new era in the surgical treatment of congenital heart disease.
As the most common cyanotic congenital heart disease, Tetralogy of Fallot accounts for about 10% of all congenital heart diseases, with approximately 70,000 newborns worldwide suffering from it each year. In developing countries, limited by medical resources, many children still face the predicament of delayed diagnosis and insufficient treatment. Today, with the advancement of surgical techniques and perioperative management, the mortality rate of TOF radical surgery has dropped from over 30% in the early days to about 1%, and the 20-year survival rate of patients is as high as 87%. This path from despair to hope is paved with the crystallization of medical wisdom and illuminates the way forward.
Tetralogy of Fallot is not a simple single defect but a set of complex cardiac malformations systematically described by French doctor Étienne Fallot in 1888, including four key features:
• Right ventricular outflow tract obstruction: Stenosis of the pulmonary valve or subvalvular muscle tissue, like a "malfunctioning valve"
• Ventricular septal defect: An abnormal channel between the left and right ventricles
• Overriding aorta: The aorta "straddles" both the left and right ventricles
• Right ventricular hypertrophy: Abnormal thickening of the right heart muscle
This special structure causes a large amount of hypoxic venous blood to mix into the systemic circulation, leading to characteristic manifestations in children: cyanosis of the skin and mucous membranes, shortness of breath after activity, stunted growth and development, and the typical "squatting phenomenon" - improving hypoxia by increasing venous return through squatting. Without timely treatment, 25% to 35% of children with severe TOF die within 1 year, 50% die within 3 years, and 90% die before the age of 10. The main causes of death include chronic hypoxia-induced heart failure, brain abscess, or infective endocarditis.
Knowledge Extension: Why are TOF children prone to brain abscess?
Long-term hypoxia increases blood viscosity, making it easy for bacteria to colonize in microthrombi; at the same time, venous blood enters the systemic circulation directly without being filtered by the lungs, allowing bacteria to reach the brain directly. In the case of a TOF child with a brain abscess reported by Sichuan 363 Hospital in 2025, the child's life was successfully saved through multidisciplinary collaboration (cardiac surgery + neurosurgery + anesthesiology) to complete a high-difficulty minimally invasive puncture.
The Blalock-Taussig shunt, as the initial life-saving surgery, establishes a "bypass channel" between the subclavian artery and the pulmonary artery to increase pulmonary blood flow and improve hypoxia. Although it is only a transitional treatment, it buys valuable time for radical surgery. Later, surgeries such as the Glenn procedure (superior vena cava-right pulmonary artery anastomosis) and the Waterston procedure (ascending aorta-right pulmonary artery anastomosis) jointly formed the early palliative treatment system for TOF.
In 1954, Dr. C. Walton Lillehei from the University of Minnesota performed the world's first radical TOF surgery using the "cross-circulation" technique - connecting the child to his father through a tube, with the father providing cardiopulmonary bypass support. Although this pioneering surgery could not be popularized due to ethical controversies, it laid the foundation for modern cardiopulmonary bypass technology. In the 1970s, with the maturity of deep hypothermia and circulatory arrest technology, radical surgery gradually developed towards younger ages, making surgery in infancy possible.
In traditional radical surgery, to relieve right ventricular outflow tract obstruction, it is often necessary to incise the annulus and implant a large patch (transannular patch), leading to severe pulmonary valve regurgitation - the right ventricle bears long-term volume overload, eventually causing progressive ventricular dilation, arrhythmia, and even sudden death. Faced with this dilemma, the team led by Chinese scholar Professor Wu Zhongshi proposed the "pulmonary valve protection strategy":
• Dredge the outflow tract through the right atrium-tricuspid valve orifice
• Sharply resect muscle tissue instead of blindly incising
• Choose individualized plans according to annulus development:
◦ Simple commissurotomy (annulus diameter ≥ 60% of expected)
◦ Balloon annuloplasty (new technology in 2014)
◦ Limited single-flap widening (annulus Z-value ≤ -4)
This strategy enabled 74% of patients to avoid transannular patches, reducing the perioperative mortality rate to 1.1% and significantly lowering the risk of long-term pulmonary regurgitation. At the same time, "valve-sparing repair (PV-SR) technology" has emerged internationally. A 2019-2023 analysis of 115 humanitarian aid children at Geneva University Hospital found that when the pulmonary valve annulus diameter ≥ 0.855 cm and Z-value ≥ -2.65, the success rate of PV-SR is significantly improved.
The current TOF treatment has formed a multi-dimensional decision-making system:
• Conservative treatment
◦ First aid for hypoxic episodes: chest-knee position → oxygen inhalation → propranolol/morphine → sodium bicarbonate to correct acidosis
◦ Preparation for elective surgery: maintain hydration, prevent infection, correct anemia
• Staged surgery vs. one-stage radical surgery
◦ Staged strategy: critically ill infants first undergo palliative shunt (such as modified Blalock procedure), followed by radical surgery 3-5 years later
◦ Trend of one-stage radical surgery: with technological progress, more centers tend to perform early radical surgery (optimal age 6-12 months)
• Philosophy of valve management
◦ Radical approach: completely resect obstructive tissue to ensure patency, accepting pulmonary regurgitation
◦ Conservative approach: carefully dissect to preserve valve function, tolerating mild residual obstruction
International differences: Europe and the United States emphasize early radical surgery, Japan tends to delay surgery; China innovatively combines balloon dilation with conservative incision to explore a "third path"
Even if the surgery is successful, some patients still face long-term challenges:
• Pulmonary valve regurgitation: with an incidence rate of up to 42%, it is the primary reason for reintervention
• Right ventricular outflow tract aneurysm: related to excessive resection of muscle bundles
• Left pulmonary artery stenosis: postoperative restenosis is like an "invisible killer", and traditional open-chest repair is highly traumatic
• Prosthetic valve endocarditis (PVE): A 2025 report from Iran described a fatal case of sudden PVE 10 years after TOF surgery. Routine blood culture was negative, and finally, 16S rRNA sequencing detected Streptococcus mitis (S. mitis), highlighting the value of molecular diagnosis in PVE
Faced with these challenges, minimally invasive technology brings hope. In early 2025, the team led by Fan Yue from Guangxi Ruikang Hospital successfully implanted a stent for a patient with left pulmonary artery stenosis after TOF surgery using intracardiac echocardiography (ICE) guidance:
1. Precise positioning: a microprobe reaches the right atrium to lock the stenotic segment
2. Real-time monitoring: monitor the entire process of balloon dilation and stent deployment
3. Immediate evaluation: confirm that the stent is well apposed and blood flow is accelerated
The application of the domestic Tingsheng Technology Sonic Eyes 10 catheter has achieved "zero radiation, low trauma" precise treatment, representing the rise of "Made in China" in the field of congenital heart disease.
A multicenter study published in July 2025 in Interdisciplinary CardioVascular and Thoracic Surgery revealed the long-term performance of artificial pulmonary valves:
• Bioprosthetic valves (BPV) have a median durability of 18.6 years
• Percutaneous valves (such as SAPIEN) have an average durability of only 9.4 years, with a reintervention risk 3.27 times that of bioprosthetic valves
• Unexpected finding: Edwards' new anti-calcification valve Inspiris Resilia performs poorly in the pulmonary position, with a significantly increased early degeneration rate within 7 years (HR=10.13)
The study also pointed out three major risk factors:
Age < 14 years (HR=5.37)
Valve size < 23 mm (HR=2.10)
Male patients (risk 1.98 times that of females)
This result provides high-level evidence for the selection of surgical timing for adolescent patients and also sounds an alarm for valve manufacturers - not all designs suitable for the aortic position are suitable for the low-pressure pulmonary artery system.
The mortality rate of Tetralogy of Fallot combined with prosthetic valve endocarditis is as high as 40%, and about 11% of cases have negative blood cultures, leading to delayed diagnosis. In the fatal case reported by the University of Tehran in 2025, the pathogen - Streptococcus mitis (S. mitis) - was identified through valve tissue 16S rRNA sequencing. This oral resident bacterium is inherently resistant to β-lactam antibiotics, and the conventional vancomycin + meropenem regimen is ineffective. This case suggests:
• Molecular diagnostic techniques (PCR/NGS) should be used as routine methods for PVE
• Prophylactic antibiotics before dental procedures are crucial for TOF patients
• DIC score ≥ 5 points requires active anticoagulant intervention
For children with delayed diagnosis in areas with scarce medical resources, Geneva University Hospital has established a PV-SR success prediction model:
Predictive Factor | Threshold | OR Value | Clinical Significance |
Body Mass Index (BMI) | ≤13.66 kg/m² | 0.711 | Nutritional intervention improves surgical feasibility |
Pulmonary Valve Annulus Diameter | ≥0.855 cm | 28.653 | Quantitative index for simple ultrasound evaluation |
Annulus Z-Value | ≥-2.65 | 1.606 | Standardized parameter after correcting body size |
This model provides a simple decision-making tool for surgical teams in regions such as Africa and the Middle East, optimizing the fairness of global TOF treatment.
The biggest pain point of current artificial valves is the contradiction between "static design" and "dynamic growth". Due to physical development, child patients need multiple surgical replacements, with a reintervention rate of up to 41% in patients under 14 years old (only 7% in adults). Promising breakthrough directions in the next decade:
• Tissue-engineered valves: equipped with stem cell technology, with self-renewal and growth potential
• Degradable stent valves: after stent absorption, leaving functional valves wrapped in autologous tissue
• 4D printing technology: implanted to gradually expand according to a preset program
The Bambino Gesù Children's Hospital in Italy is carrying out the "Living Valve Project", expecting to achieve the ultimate goal of "one replacement for a lifetime" through 3D bioprinting combined with the patient's autologous cells.
With the development of genetic technology, the prevention and treatment of TOF have been advanced:
• High-risk family screening: gene mutations such as NKX2-5 and GATA4 have been found to be related to TOF
• Fetal cardiac intervention: intrauterine balloon dilation to relieve pulmonary artery obstruction and promote pulmonary vascular development
• Epigenetic regulation: reducing right ventricular fibrosis through methylation modification
China's "14th Five-Year Plan" for birth defect prevention and control has listed the "congenital heart disease gene map" as a key project, with the expectation of completing 50,000 whole-genome sequencings by 2030.
• AI surgical navigation: real-time quantification of resection range, balancing "obstruction relief" and "valve protection"
• Digital twin heart: individualized simulation of hemodynamics to predict long-term complications
• Global TOF registration system: integrating multi-center data to dynamically update treatment guidelines
Ethical challenge: How to choose when AI recommends conservative treatment but the family requests radical treatment? This suggests that technology needs to be combined with humanistic care.
From Dr. Blalock's tweezers from the jewelry store in 1944 to today's nanoscale operations under ICE guidance; from a desperate mortality rate of 30% to a long-term survival rate of over 90% - the treatment history of Tetralogy of Fallot is an epic of the integration of medical technological breakthroughs and humanistic care.
When we see Ningning's smile after being discharged three days after the operation, or read about African children receiving PV-SR surgery through humanitarian aid, we deeply understand that every continuation of a heartbeat is the highest praise for life.
The future has arrived. With the joint efforts of global medical workers, "growth-enabled valves" will come true from dreams, gene editing technology is expected to rewrite the disease script, and digital healthcare will weave a borderless life protection network. As Professor Wu Zhongshi said: "What we repair is not just the heart, but also the life bound by the disease". This "path of life" opened with wisdom and compassion will never close.
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