Long-term survival of patients with unoperated single ventricle heart defect: Four case reports and literature review

A single ventricle (SV) heart defect is a rare complex congenital cardiac malformation, accounting for approximately 1% – 2% of congenital heart diseases. Surgical intervention is the mainstay treatment for SV patients, although patients who do not receive surgical intervention may also survive. We followed up four adult patients who had SV since birth without surgical intervention and they had a good prognosis. The common characteristics of four long-term SV survivors were investigated by reviewing their medical records and the literature, and the current treatment methods for SV patients were also reviewed. The clinical presentation and long-term prognosis of SV patients without surgical intervention depend on the presence or absence of pulmonary blood flow obstruction, pulmonary vascular resistance, ventricular shape and function, aortic blood flow obstruction, and the atrioventricular valve shape and function. While the Fontan operation has become a common and effective method for SV treatment, long-term outcomes are fraught with morbidity and mortality. In our opinion, such patients with balanced hemodynamic condition could be followed and treated conservatively. Major cardiac surgery which leads to gross hemodynamic adjustments should be avoided. However, additional prospective study will be necessary to verify this assertion. This report aims to improve the prognosis as well as quality of life of SV patients.


| INTRODUCTION
A single ventricle (SV) heart defect is a rare complex congenital cardiac malformation, accounting for approximately 1%-2% of congenital heart diseases. 1 SV is more commonly referred to as two-sided atrioventricular valves or a common atrioventricular valve opening in one ventricle. Patients with SV have only one functional ventricular chamber, and blood from the body and pulmonary circulation is mixed in the heart chamber, often causing overload in the single functional ventricular chamber and leading to heart failure in the early stages. 2 Surgical intervention is the mainstay treatment for SV patients, although patients who do not receive surgical intervention may also survive. For example, it was reported that among unoperated patients with single-ventricular hearts, the first-year survival rate was 10%-30%, with a median survival of 14 years. 3 In this study, we report four adult patients who had SV since birth without surgical intervention and survived to adulthood. All the cases information and the images (  in this review have been approved by the ethics committee of our hospital. We also conducted a Medline search and reviewed similar cases published in recent years. In addition, we summarized the influence of treatment methods on the survival rate of SV patients in recent years.

| Case 1
A 13-year-old female patient (height:150 cm; weight: 42 kg) was diagnosed with functional SV combined with transposition of the great arteries (TGA) with a right position of the aorta based on ultrasound findings at the age of 3, but did not receive any treatment. In 2017, she came to our hospital due to numbness in both lower limbs and dyskinesia. Thoracic magnetic resonance imaging showed a spaceoccupying lesion in the spinal canal. A bone biopsy was performed and revealed cavernous hemangioma. This patient underwent a tumor resection at another hospital and returned to our hospital for radiotherapy 5 months after the operation.
Physical examination at our hospital showed a temperature of 36.5 C, a pulse of 80 beats/min, no difference in the pulse and heart rate, and a blood pressure of 120/80 mmHg. Other pertinent examinations showed no signs of anemia and she had no history of hemoptysis, syncope, or long-term high fever. Her New York Heart Association functional class was II. Echocardiography revealed the following: the heart was located in the left thoracic cavity, the atrium was in the normal position, the left ventricular cavity was the main cavity, and the right ventricular cavity was the residual cavity. The pulmonary artery (PA) was located on the posterior side and arose from the autonomous cavity. The aorta was moderately developed, located on the anterior side and arose from the self-mutilating cavity. Echocardiography demonstrated interrupted ventricular septal echo ( Figure 1). Color Doppler flow imaging (CDFI) revealed a bidirectional low-resistance shunt in the ventricular septal defect. The patient was diagnosed with the following diseases based on the echocardiography results: congenital heart disease, functional SV, TGA, ventricular septal defect, mild pulmonary valve stenosis (PS), left ventricular hypertrophy, and left atrial enlargement. Further examination was recommended. No tumor metastasis was found after radiotherapy at our hospital and the prognosis was appreciable.

| Case 2
A 41-year-old female patient (height: 163 cm, weight: 53 kg) was admitted to our hospital due to chest pain, chest tightness, and palpitations lasting for 3 days. She presented with cyanosis of the mouth and limb immediately after birth, with obvious cyanosis after crying but without syncope or squatting signs. She was diagnosed with a congenital heart disease at the local hospital but was not treated. Her growth and development were not affected and daily activities were only slightly limited. After catching a cold 3 days earlier, she experienced chest tightness and shortness of breath after general physical activities. After symptomatic treatment at the local hospital, she was admitted to our hospital due to a lack of obvious symptom relief.
Physical examination at our hospital revealed a temperature of 36.6 C, a pulse of 62 beats/min, the moist rales could be heard in both lungs. Her New York Heart Association functional class was III.
Echocardiography showed visceral antipositioning and dextrocardia as well as a heart with a functional single atrium and SV, ventricular hypertrophy, and a common atrioventricular valve. Two large arteries, the PA and the aorta, were concomitant, both starting from the functional SV. The PA was located on the anterior side, the inferior valve had muscular stenosis, and the aorta was located on the posterior side. No obvious abnormalities were found in the aortic valve. CDFI The echocardiographic diagnosis for this patient was congenital heart disease complex deformity, dextrocardia, single atrium, SV, PS, and severe common atrioventricular valve insufficiency. The patient was discharged after 5 days of antiinfection and symptomatic treatments.
After discharge, we continued to follow up with the patient by telephone and outpatient visits.

| Case 3
A 13-year-old female patient (height: 149 cm; weight: 40 kg) came to our hospital due to palpitations and chest tightness lasting for 2 days.
She was diagnosed with a complex congenital heart disease at the age of 6 months but was not treated. Physical examination on admission showed a body temperature of 36.4 C, a pulse of 57 beats/min, and a blood pressure of 105/70 mmHg. Her New York Heart Association functional class was II. Echocardiography showed the following: the heart was located in the left thoracic cavity, the atrium was in the normal position, the PA and the aorta were concomitant, and the PA was located in front of the aorta, both starting from a functional SV. The right atrium was enlarged, no atrioventricular valve was found in the left ventricular cavity parallel to the right atrium. Echocardiography demonstrated interrupted atrial septal echo and the internal diameter of the SV was 65 mm. CDFI showed a shunt in the atrial septal defect with a flow rate of 2.6 m/s and a PG of 29 mmHg. There were severe reflux in the atrioventricular valve in the systolic stage, the regurgitation area of the atrioventricular valve orifice was 3.7 cm 2 , the flow rate was 5.4 cm/s, and the PG was 117 mmHg (Figure 4). The length of the pulmonary valve regurgitation beam was 22.8 mm, the flow rate was 3.5 m/s, the PG was 50 mmHg, and the average PA pressure was estimated to be 55 mmHg. The echocardiographic diagnosis was congenital heart disease (SV, atrial septal defect), mild atrioventricular valve insufficiency, mild pulmonary valve regurgitation, and pulmonary hypertension (PH). The patient was discharged after 3 days of symptomatic treatment.

| Case 4
A 39-year-old woman (height: 162 cm; weight: 57 kg) came to our hospital for chest pain and chest tightness lasting for 4 days. She was diagnosed with a congenital heart disease at birth but was not treated. Unlike echocardiography, three-dimensional ultrasound can visually display the internal structure of the heart, thus improving the accuracy of preoperative diagnosis, and is of great significance in the selection of surgical methods and the assessment of prognosis. 6 We reviewed literature reports of SV heart defect cases involving patients over 13 years of age without surgical intervention and summarized the common characteristics that were correlated to the long-term survival of the patients (

| Drug treatment
The level of pulmonary vascular resistance in SV patients is the key to determine the long-term postoperative efficacy. 20 Nine drugs have been approved for the treatment of PH. These drugs fall into four categories: 5-phosphodiesterase inhibitors such as sildenafil and udenafil, endothelin receptor antagonists like bosentan and ambrisentan, prostacyclin analogues, and soluble guanosine activators. A study showed that a single dose of sildenafil improved the peak exercise performance in Fontan patients compared with a placebo. 21 It is reported a lower pulmonary arterial pressure after short-term postoperative administration of sildenafil, whereas no significant differences in sildenafil, bosentan, or beraprost sodium. 22,23 Bosentan is currently controversial in raising the NYHA rating. 24 There is little evidence to support the use of angiotensin-converting enzyme inhibitors for SV patients. 25

| CONCLUSION
With the development of new surgical methods for the treatment of SV heart defects, it is important to understand the long-term outcomes for patients who have not been operated on. 26 While the Fontan operation has become a common and effective method for SV treatment, long-term outcomes are fraught with morbidity and mortality. The majority of patients in our series and in the literature to demonstrate advanced survival had double inlet left ventricle and PS. In our opinion, such patients with balanced hemodynamic condition should be followed and treated conservatively. Major cardiac surgery which leads to gross hemodynamic adjustments should be avoided. 27 The optimal timing for surgery and appropriate surgical method can be determined based on: (1) the patient's symptoms and specific diagnosis of SV heart defect, and (2) the following conditions: the anatomy of the parting and concurrent heart malformations, the development of the PA, the amount of pressure and resistance, and ventricular function, with a significant aim to improve the prognosis as well as quality of life of SV patients.

CONFLICT OF INTEREST
The author(s) declare(s) that there is no conflict of interest.

DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.