Single Ventricle Palliation in a Developing Sub-Saharan African Country: What Should be Improved?

Abstract

Introduction:

Single ventricle physiology management is challenging, especially in low-income countries.

Objective:

To report the palliation outcomes of single ventricle patients in a developing African country.

Methods:

We retrospectively studied 83 consecutive patients subjected to single ventricle palliation in a single center between March 2011 and December 2017. Preoperative data, surgical factors, postoperative results, and survival outcomes were analyzed. The patients were divided by palliation stage: I (pulmonary artery banding [PAB] or Blalock–Taussig shunt [BTS]), II (Glenn procedure), or III (Fontan procedure).

Results:

Of the 83 patients who underwent palliation (stages I-III), 38 deaths were observed (31 after stage I, six after stage II, and one after stage III) for an overall mortality of 45.7%. The main causes of operative mortality were multiple organ dysfunction due to sepsis, shunt occlusion, and cardiogenic shock. Twenty-eight survivors were lost to follow-up (22 after stage I, six after stage II). Thirteen stage II survivors are still waiting for stage III. The mean follow-up was 366 ± 369 days. Five-year survival was 28.4 % for PAB and 30.1% for BTS, while that for stage II and III was 49.8% and 57.1%, respectively. Age (hazard ratio, 0.61; 95% confidence interval: 0.47-0.7; P = .000) and weight at surgery (hazard ratio, 0.45; 95% confidence interval: 0.31-0.64; P = .002) impacted survival.

Conclusion:

A high-mortality rate was observed in this initial experience, mainly in stage I patients. A large number of patients were lost to follow-up. A task force to improve outcomes is urgently required.

Keywords

single ventricle Fontan procedure Glenn procedure Blalock–Taussig shunt pulmonary artery banding

Introduction

The care of patients with congenital heart disease (CHD) in low-income countries has improved, leading to increased survival and better quality of life.^1

-5 Despite this progress, the postoperative care and mortality and morbidity rates of complex CHD remain challenging.^1,3,4

Single ventricle physiology, one of the main complex CHD types, requires early detection and referral to a pediatric cardiac center.^6,7 The surgical treatment of these patients usually requires more than two palliative procedures.

During the neonatal period, most patients require some form of palliation to regulate systemic arterial and pulmonary arterial blood flow. This usually includes a systemic pulmonary shunt (Blalock–Taussig shunt [BTS] or pulmonary artery banding [PAB]). Procedures like atrial septal defect enlargement, pulmonary artery reconstruction/enlargement, the Damus-Kaye-Stensel procedure, or the Norwood procedure may be necessary.⁷

After 3 months of age, single ventricle patients may undergo a bidirectional Glenn procedure. After 18 months of age, the cavopulmonary connection may be completed via the Fontan procedure.⁷

Several studies conducted in middle- and high-income countries measured survival in single ventricle palliation and reported a survival >70% after more than 15 years of follow-up.^6

-13

In low-income countries, information is lacking regarding the management of single ventricle palliation.^5,11,14 The aim of this study was to report the outcomes, survival, and management challenges of single ventricle patients in the context of a new sub-Saharan African cardiothoracic center.

Patients and Methods

The Cardio-Thoracic Center of Clínica Girassol, previously described, was created in 2011.³ Before its creation, few patients with CHD were treated abroad at an expensive cost supported by the government. With the aim to increase the number of treated patients, reduce financial costs, develop permanent and local diagnostic clinics, and train local national teams in this area, the Sociedade Nacional de Combustíveis de Angola (SONANGOL) collaboration initiative (state company responsible for oil and natural gas resources) of the Angolan Ministry of Health established a partnership program with the Portuguese Red Cross Hospital located in Lisbon, Portugal. Briefly, the Center’s infrastructure includes a dedicated fully equipped operating room for cardiac surgery, 12-bed pediatric intensive care unit (ICU), 16-bed neonatal ICU, and 20-bed ward.

The Center also has a cardiac catheterization laboratory; 256-slice computed tomography scan facility; 3 T magnetic resonance image facility; an echocardiography laboratory for two-dimensional and three-dimensional, transesophageal, fetal, and Doppler procedures; and an electrophysiology laboratory allowing full evaluation and treatment of any kind of heart disease except heart and lung transplant but including extracorporeal membrane oxygenation management equipment for any age-group.

Here, we conducted a retrospective analysis of the electronic records of all patients with single ventricle physiology younger than 18 years of age who received surgical palliation at this Cardio-Thoracic Center between March 2011 and December 2017. Institutional review board permission was obtained.

Demographic variables including sex, age at surgery, weight, diagnosis, others associated with CHD, palliation stage, concomitant procedures, mechanical ventilation time, ICU length of stay (LOS), total hospital LOS, operative mortality, and survival to hospital discharge were analyzed.

Operative mortality was defined as all deaths, regardless of cause, occurring during the hospitalization in which the operation was performed, even if after 30 days or all deaths, regardless of cause, occurring after discharge from the hospital, but before the end of the 30th postoperative day.

Late mortality was defined as any deaths (from any cause) of patients in the present cohort that do not meet the above-described definition of operative mortality, whether they occur at home, or during a subsequent hospitalization, or at any other location.

Surgical palliation was considered one of the following procedures. Systemic-pulmonary shunt (BTS or central shunt) and PAB were included in stage I. Stage II involved the Glenn procedure with or without associated procedures, while stage III included the Fontan procedure. The sample was divided into three stages according to palliation stage.

Effective PAB was considered when the saturation was 85% to 90%, and the transpulmonary gradient was >50 mm Hg. A gradient >80 mm Hg and saturation <85% was considered tight, whereas a gradient <50 mm Hg and saturation >95% was considered loose.

Blalock–Taussig shunt size was calculated by patient body surface area. Patients with BTS received acetylsalicylic acid daily for 1 month (10 mg/kg). Echocardiography was performed for all patients at every visit.

The follow-up time was defined as the time (days) between the operation and the last recorded outpatient visit. Patients were followed up at outpatient clinics. Near the date of the consultation, previously scheduled patients were contacted by telephone.

Lost to follow-up was considered no attendance for at least two outpatient visits. Only 66.3% (n = 55) of patients completed the mean follow-up of 366 ± 369 days. Twenty-two (33.8%) stage I survivors and six (20%) stage II survivors were lost to follow-up.

Statistical Analysis

Standard descriptive statistics were calculated. Continuous numerical variables are presented as median and interquartile range (IQR: 25th-75th percentiles). Survival was estimated using Kaplan-Meier curves. For the univariate risk analysis and the multivariate analysis, we used the Cox proportional hazard regression model to establish the variables that were independently predictive of mortality. To estimate the association between independent and dependent variables, the hazard ratio (HR) risk measure was used with the 95% confidence interval (CI). The level of statistical significance was P = .05. The data were analyzed using IBM SPSS version 23.0 (IBM Corp, Armonk, New York).

Results

The patients’ demographics data are illustrated in Tables 1 and 2. None had a prenatal diagnosis and few had an early diagnosis, major chromosomal abnormality, or major noncardiac structural anomaly. Patients underwent PAB at a median age of 135 (IQR: 63-201) days and median weight of 5 kg (IQR: 4-7). Among patients who underwent BTS, the median age was 100 (IQR: 39-128) days, weight was 4 kg (IQR: 4-5). The patients who underwent the Glenn procedure were a median age of 410 days (IQR: 302-739) and median weight of 8 kg (IQR: 7-10). As expected, patients undergoing the Fontan procedure were older, with a median age of 1415 days (IQR: 146-1,534) and median weight of 17 kg (IQR: 8-20).

Table 1.

Preoperative Patients’ Characteristics of 83 Patients Who Underwent Palliation From March 2011 to December 2017.

Variable	PAB (34)	BTS (31)	Glenn Operation (30)	Fontan Operation (5)
Sex, M:F	20:14	10:21	18:12	3:2
Age (days)
<30	3	7	2	0
30-365	24	20	12	0
>365	7	4	16	5
Weight (kg; median)	5	4	8	17
Diagnostic
Tricuspid atresia	14	22	20	3
Double inlet LV	2	0	1	0
Double outlet RV	6	0	0	0
TGA	1	0	1	0
Unbalanced AVSD	3	1	2	1
Mitral atresia	1	1	1	1
Others	7	7	3	0
Ventricular dominance
Right ventricle	12	3	4	1
Left ventricle	21	28	26	4
Biventricular	1	0	0	0
Associated CHD	23	23	20	4

Abbreviations: AVSD, atrioventricular septal defect; CHD, congenital heart disease; BTS, Blalock–Taussig shunt; F, female; LV, left ventricle; M, male; PAB, pulmonary artery banding; RV, right ventricle; TGA, transposition of the great arteries.

Table 2.

Postoperative Patients’ Data of 83 Patients Who Underwent Palliation From March 2011 to December 2017.

Variable	PAB (34)	BTS (31)	Glenn Procedure (30)	Fontan Procedure (5)
Mechanic ventilation (hour)	7 (4-7)	9 (5-16)	7 (6-9)	9 (7-14)
ICU stay (days)	2 (1-4)	2 (1-5)	2 (1-4)	3 (2-5)
Total hospital stays (days)	7 (5-7)	7 (5-10)	8 (6-10)	10 (9-14)
Interval interstage	246	246	1018
Mortality	10	21	6	1

Abbreviations: BTS, Blalock–Taussig shunt; ICU, intensive care unit; PAB, pulmonary artery banding.

Outcomes

The status of all 83 patients enrolled in the study is summarized in Figure 1. The study cohort consisted of 65 stage I patients and 30 stage II patients. Twelve patients were enrolled as stage II candidates from onset. Only five of the stage II patients have undergone the Fontan procedure with 13 still awaiting the procedure. The median interval between stages I and II was 246 days (IQR: 187-310 days) and between stages II and III was 1.018 days (IQR: 214-0).

At the stage I level, 34 patients underwent PAB with an operative mortality of 11.8% (four deaths), mechanical ventilation time of seven hours (IQR: 4-12 hours), ICU LOS of 2 days (IQR: 1-4 days), and total hospital LOS of seven days (IQR: 5-12 days).

Among 31 patients who underwent BTS, the operative mortality was 45.2% (14 deaths). The mechanical ventilation time was nine hours (IQR: 5-16 hours), ICU LOS was two days (IQR: 1-5 days), and total hospital LOS was seven days (IQR: 5-10 days).

Thirty stage II patients underwent the Glenn procedure with an operative mortality of 16.7% (five deaths). Eighteen (60%) of the 30 underwent the Glenn procedure as the primary operation; the remaining 12 (40%) previously underwent a PAB⁹ or a BTS.³ Mechanical ventilation time was seven hours (IQR: 6-9 hours), ICU LOS was two days (IQR: 1-4 days), and total hospital LOS was eight days (IQR: 6-10 days).

Five patients underwent the Fontan procedure with an operative mortality of 20% (one death). Mechanical ventilation time was nine hours (IQR: 7-14 hours), ICU LOS was three days (IQR: 2-5 days), and total hospital LOS was ten days (IQR: 9-14 days).

Late mortality occurred in 14 patients: six after PAB, seven after BTS, and one after Glenn shunt.

Cause of Death

A total of 38 deaths (45.7% of 83 patients) occurred in three stages. Twenty-four were operative mortality and 14 were late mortality. The main causes of operative mortality were multiple organ dysfunction due to sepsis, shunt occlusion, and cardiogenic shock (Table 3). No postmortem examinations were performed of these patients. Causes of death of late mortality (14 patients) were unknown.

Table 3.

Cause of Operative Mortality of 24 Patients With Single Ventricle Physiology Who Underwent Palliation From March 2011 to December 2017.

Cause of Death	Frequency
Cause of Death	BTS	PAB	Glenn Procedure	Fontan Procedure	Total
Multiple organ dysfunction due to sepsis	4	3	-	-	7
Shunt occlusion	5	-	-	-	5
Cardiogenic shock	1	1	2	1	5
Asphyxia (bronchoaspiration)	3	-	-	-	3
Stroke	1	-	1	-	2
Chylothorax	-	-	2	-	2
Total	14	4	5	1	24

Abbreviations: BTS, Blalock–Taussig shunt; PAB, pulmonary artery banding.

Survival

Survival by stage is summarized in Figures 2 to 4. In stage III, estimated actuarial survival at 30, 365, and 730 days was 85.7% and the curve stabilized at 57.1%. The results of Cox regression analysis of overall mortality showed that it was more likely to occur in females (55.3% vs 42.2%; P = .11), older patients (129 [IQR: 65-230] vs 64 [IQR: 63-564] days; P = .18), heavier patients (4 [IQR: 4-6] vs 7 [IQR: 4-9]; P = .03), those with left ventricle dominance (76.3% vs 84.4%; P = .35), and those with an associated CHD (61 vs 22; P = .23).

Median age and weight impacted the survival of patients in stage I (HR: 0.61; 95% CI: 0.47-0.7; P = .000; and HR: 0.45; 95% CI: 0.31-0.64; P = .002), respectively. No statistically significant difference was noted in ICU or hospital LOS (P = .07 and .25, respectively) neither for left ventricle dominance (HR: 1.4; 95% CI: 0.33-6.35; P = .60).

Comment

Infants with single ventricle physiology are at high risk of death during the first years of life. Five-year survival without any surgical intervention is around 20%.¹⁵ Although one cannot offer anatomical correction, surgical palliation offers significantly improved survival and quality of life for these patients. Several studies have reported >70% survival rates.^6

-13 In contrast, operative mortality was very high in this study. Most of the deaths in our study occurred during hospitalization at stage I, mainly in patients who underwent BTS. Although it is known that patients with single ventricle physiology are at a three-fold higher risk of death after BTS, our result are very high compared to those in the current literature.^16

-20 This result is attributed to the continuous forward flow of blood into the pulmonary artery during systole and diastole, which may cause myocardial ischemia and circulatory instability due to coronary steal, particularly for low-weight infants who undergo BTS under cardiopulmonary bypass.^16
-18

In our cohort, the most common causes of death were multiple organ dysfunction due to sepsis, shunt occlusion, cardiogenic shock, and asphyxia by broncoaspiration. A more rigorous infective preoperative screening, preoperative respiratory physiotherapy, first track extubation (reducing pulmonary infection), and protocol to reduce the incidence of surgical site infections should be provided. In addition, close nursing care should be provided in the ICU and the ward to avoid further cases of broncoaspiration.

A high number of BTS occlusions was observed. Thrombotic episodes are common in patients with cyanotic heart diseases and can lead to shunt occlusion. The use of prosthetic material as in modified BTS warrants anticoagulation/antiaggregation platelets. Anticoagulation is commonly used but its impact has not been established.²¹ Our patients usually take acetylsalicylic acid 10 mg/kg daily for one month. The high number of occlusions can also be associated with surgical technique. Another hypothesis is an association with hemoglobinopathy given the fact that Angola has one of the highest prevalence rates of hemoglobinopathy in the continent.²² A study of patients with concomitant cyanotic CHD and hemoglobinopathy should be conducted. Cardiogenic chock was attributed to late diagnosis (ventricular dysfunction) as demonstrated in the results section, as none of the patients had a prenatal diagnosis and few had an early diagnosis.

The diagnosis of CHD in developing countries is late compared to that in developed countries.^14,23 In sub-Saharan Africa, these problems are even more prominent. In Angola, <5% of CHD cases are diagnosed before 30 days of life.^2,3 In Mozambique, approximately 50% of patients were diagnosed with a cardiac malformation at >2 years of age.¹ A recent national Nigerian pediatric cardiac registry showed that only 14% of diagnoses occurred before 30 days of life.²⁴ Multiple factors, such as a lack of an adequately trained health system and socioeconomic constraints are responsible for the delay.²⁵

An alternative is the implementation of pulse oximetry screening immediately postbirth as is done in many countries.^25,26 The use of telediagnosis with fetal cardiac ultrasound image transmission is another alternative that can increase early diagnosis in >50% of cases.^27,28 An efficient and more comprehensive national referral system should be developed. To date, the referral system encompasses preevaluation of patients principally at the main Pediatric Hospital in Luanda (capital) to the Cardio-Thoracic Center of Clínica Girassol. Based on these results, we suggest the creation of a national electronic list for the regulation of cardiac surgeries managed by the pediatric cardiothoracic center.

In cases in which patients died after discharge, we speculate that other noncardiac causes of deaths can explain the high 30-day postoperative mortality, such as malaria, acute diarrheal disease, malnutrition, pneumonia, HIV, sepsis, meningitis, tetanus, and bronchial aspiration asphyxia. Angola has one of the highest infant mortality rates on the continent due to the reasons mentioned above.^29,30 Our patients are exposed to those conditions, which could cause the high mortality rates. Despite the government investments to care for patients with CHD, continuous improvements in the health of pregnant women and new mothers will play an important role in further reducing child mortality rates.

Several studies have pointed out that right ventricular dominance is associated with a worse result.^7,31 In the present study, the opposite was observed, although the difference was not statistically significant. Most deaths in stage I occurred in patients with left ventricular dominance, although the difference was not statistically significant. We believe that the main reasons were a late diagnosis, poor perioperative care, outpatient follow-up, low weight, and low experience of the cardiac team, as pointed out by other authors.^7,32-33 In addition to high mortality, we observed significant stage I patient loss to follow-up.

To date, patients have been followed at the outpatient clinic and by phone. This way, we have lost several patients. In Angola, associated with geographical access, financial access, and parents lacking understanding of their child’s condition, it is common for people to lose or change their cell phone number as well as their home address, which makes follow-up difficult. Thus, a new strategy is required. To compound the problem, the number of patients living outside of the capital is increasing, and most provinces do not have pediatric cardiologists.

We propose parental education on CHD to clarify the complexity of the disease and remind parents to call whenever necessary or to report updated addresses and phone numbers. A task force with pediatricians and adult cardiologists would allow all provinces to follow-up on patients together and scheduling visits for each province. Thus, such a notion would encourage the training of national professionals specializing in the care of patients with CHD.

Higher survival and lower mortality rates were observed in stage II compared to stage I. However, the mortality of patients undergoing the Glenn procedure in the literature is around 4%,⁷ while that in our study was 20%. The Glenn procedure as the first palliative procedure reportedly has good results.^5,18 Thus, it can be an option for our patients.

Conclusion

Progress in the care of patients with CHD in sub-Saharan African countries has been observed. However, high mortality and loss to follow-up continue to be a big challenge, especially for cases of complex CHD consisting of single ventricle physiology. Rigorous infection control pre-, intra-, and postoperative are required. Early diagnosis and the creation of a network that allows easy and early referral from primary health-care units to the surgical center are necessary. A study of patients with CHD and hemoglobinopathy should be conducted. Use of the Glenn procedure as the first surgery should also be considered. A task force to decrease loss to follow-up is urgently required and may improve the outcomes of patients with single ventricle physiology in sub-Saharan Africa.

Limitation

One of this study’s main limitations was its retrospective nature, while another was its short follow-up period.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Valdano Manuel, MD

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