¹Department of Vascular Surgery, Al-Thawra Modern General Hospital, Sana'a, Yemen

²Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen

³Department of General Surgery, Al-Thawra Modern General Hospital, Sana'a, Yemen

⁴Department of Clinical Pharmacy and Pharmacy Practice, University of Science and Technology, Sana'a, Yemen

⁵Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia

*Corresponding author: Abdulsalam M Halboup, Department of Clinical Pharmacy and Pharmacy Practice, University of Science and Technology, P.O. Box13064, Sana’a, Yemen, Tel:+967774960247; E-mail: [email protected].

Received Date: December 18, 2023

Published Date: December 29, 2023

Citation: Al-Madwahi NY, et al. (2023). Evaluating the Clinical Outcomes of Patent Ductus Arteriosus Surgical Closure in Yemeni Patients: A Retrospective Single-Center Study. Mathews J Surg. 6(4):25.

Copyrights: Al-Madwahi NY, et al. © (2023).

ABSTRACT

Background: Patent ductus arteriosus (PDA) surgical closure is a standard treatment approach for symptomatic neonates unresponsive to medical therapy. However, limited data on outcomes exist, particularly in resource-limited settings like Yemen. Purpose: This study aimed to evaluate isolated PDA surgical closure outcomes, including intensive care unit (ICU) stay, extubation, hospitalization, and postoperative complications. Methods: A retrospective study was conducted from May 2017 to May 2022 at Al-Thawra Modern General Hospital. Transthoracic echocardiography confirmed PDA diagnosis and assessed pulmonary hypertension severity. Results: A total of 290 patients underwent PDA closure, with the majority being female (65.5%, n=190) and infants (65.5%, n=190). The majority had moderate to severe pulmonary hypertension (61%, n=177). Primary intervention was PDA ligation with hemoclip application (82.1%, n=238). Most patients were extubated in the ICU (78.6%, n=228), discharged on the 5^th day or earlier (90.3%, n=262), and 71% (n=206) required more than 12 hours in ICU. Complications occurred in 7.2% (n=21) of the cases, primarily residual duct issues and recurrent laryngeal nerve complications. Three cases (1.0%) resulted in non-surgery related deaths. Pulmonary hypertension significantly influenced hospital stay, extubation, and postoperative complications. Conclusion: Surgical PDA closure is safe and effective in Yemen. Pulmonary hypertension significantly influences outcomes, highlighting the importance of early detection and timely PDA management to prevent complications.

Keywords: Patent Ductus Arteriosus, Congenital Heart Defects, Infants, Yemeni Patient.

INTRODUCTION

Patent ductus arteriosus (PDA) is a frequently encountered cardiovascular anomaly, and its presence is linked to unfavorable short-term and long-term consequences. These include the development of feeding difficulties, necrotizing enterocolitis, intracranial hemorrhage, reduced glomerular filtration rate, and bronchopulmonary dysplasia [1-4]. Preterm newborns have higher incidence of PDA since the normal physiological mechanisms that contribute to PDA closure, such as oxygen tension and decreased prostaglandins, are altered in premature infants [5]. Evidence revealed that the occurrence of PDA inversely linked to gestational age and weight [6].

Surgical PDA closure becomes necessary when symptomatic manifestations persist or medical treatment fails [7,8]. Even asymptomatic patients with considerable left-to-right shunting are recommended for closure to prevent future complications [9]. The outcomes of PDA closure have shown favorable results, particularly in cases with mildly elevated pulmonary vascular resistance and even some individuals with Eisenmenger's syndrome [10]. Closure reduces pulmonary blood flow and artery pressure, even in the presence of persistently high pulmonary vascular resistance [11]. However, the indications for closing small shunts, including those incidentally found ("silent"), particularly in older patients, remain less certain [12,13].

Given the advances in medical technology and surgical expertise, complications such as injury to the recurrent laryngeal nerve, chylothorax, residual duct, subcutaneous emphysema, and subcutaneous hematoma remain possible outcomes [14-16]. Moreover, transcatheter technique is expensive and requires a significant level of expertise [17].

This study focuses on the unique context of Yemen, a developing country in the middle east, where more than 80% of the population is estimated to live below the poverty line, and the ongoing conflict has further fractured the healthcare system [18-20]. Previous studies focused on the prevalence of congenital heart diseases [21-24]. However, a notable gap exists in understanding post-surgical outcomes of PDA closure. Therefore, the study aimed to evaluate the short-term surgical outcomes of PDA closure in Yemeni patients, focusing on postoperative complications, critical care duration, hospitalization length, and extubation location following various PDA ligation interventions.

MATERIALS AND METHODS

Study Design and setting

This retrospective single-center study was conducted at the Cardiac Center of Al-Thawra Modern General Hospital (TMGH) during the period from May 2017 to May 2022. This hospital has 876 beds capacity and serves as the largest referral facility in Yemen's capital, Sana'a, acting as the primary destination for patients from all governorates.

Study Population

The medical records for all patients who were admitted to the cardiac center at TMGH for congenital cardiovascular anomalies within the study period were reviewed. Participants undergoing surgical intervention for isolated PDA were included. The study excluded individuals who had PDA accompanied by additional congenital cardiovascular anomalies. Preoperative confirmation of PDA diagnosis and assessment of pulmonary hypertension severity were performed using transthoracic echocardiography and clinical findings.

Sample Size and data collection method

The study included 290 patients admitted and underwent surgical intervention for isolated PDA at the TMGH cardiac center over a 5-year period. Data collection from patients' medical files included sociodemographic information, comorbidities, type of interventions, extubating location, ICU stay, hospitalization duration, and complications.

Surgical interventions

Patients were positioned in a right lateral decubitus position. A skin incision was made along the posterolateral area of the left chest, just below and running parallel to the inferior border of the scapula. The incision traverses through the latissimus dorsi and the posterior part of the serratus anterior muscle. The ribs were counted accurately and gained access to the fourth intercostal space. The left lung was gently retracted anteriorly to reveal the descending aorta. Subsequently, the mediastinal pleuron over the descending aorta was carefully opened, exposing the vagus nerve and the recurrent laryngeal nerve traversing over the ductus. Following thorough dissection, the ductus was then closed using one of the following methods:

Simple ligation: closing the duct by using silk suture Mersilk® (Ethicon, Johnson & Johnson) and polypropylene suture (PROLENE^TM 5–0 or 4-0, Ethicon Inc.). By using proline sutures, we made purse string at the end-sides of PDA; near to aortic and the pulmonary sides, and then we did simple ligation by using the silk suture in between previously purse string.

PDA ligation with hemoclip Application: closing the duct by using simple ligation as early described in addition to application of one or two medium-large titanium clips (Vitalitec International, Inc., France) in between the silk sutures.

PDA ligation with division: closing the duct by using simple ligation in addition to applying the cross-clamping at the end sides of PDA for bleeding control, followed by transection of the midpoint of PDA using proline 5-0 or 4-0.

The mediastinal pleura covering the descending aorta were precisely sealed. Subsequently, the lung was permitted to re-expand, and a small chest tube was inserted in all patients. The chest was closed using peri-costal absorbable sutures (VICRYLTM 1 or 2, polyglactin 910, Ethicon Inc.). The choice between sutures was based on the patients' requirements and the specific surgical case details. The muscle layers were carefully brought together using an absorbable suture technique, followed by the closure of the skin.

Data analysis

Data were imported into IBM SPSS Statistics version 27.0 for Windows® (IBM Corp., Armonk, NY, USA). Categorical variables, including age, gender, and PDA closure method were presented as frequencies and percentages. Outcome measures, such as ICU length of stay, overall hospital stay, extubation location, and postsurgical complications, were analyzed for associations with other independent variables (e.g., clinical and socio-demographic patient data) using chi-square and Fisher's exact tests where appropriate. A significance level of association was defined at a P-value of less than 0.05.

RESULTS

Table 1 shows the characteristics of the participants in the study. Regarding the age distribution, the majority of participants were infants (65.5%, n=190), followed by children (17.6%, n=51), and neonates (16.9%, n=49). Gender distribution showed 65.5% females (n=190) and 34.5% males (n=100). The most common type of operation was PDA ligation with hemoclip application (82.1%, n=238), followed by simple ligation (16.2%, n=47).

Analysis of PDA diameter showed that 53.4% (n=155) had a moderate diameter, 29.7% (n=86) had a large diameter, and 16.9% (n=49) had a small diameter. Pulmonary hypertension was diagnosed in all patients, with 61.0% (n=177) experiencing moderate severity and 39.0% (n=113) having mild to moderate pulmonary hypertension. The majority were extubated in the ICU (78.6%, n=228), and 71.0% (n=206) stayed more than 12 hours in the ICU. A large proportion (90.3%, n=262) was discharged on the 5^th day or earlier. Post-operative complications were observed in 7.2% of cases (n=21), with the most common issues being residual duct problems (28.6%, n=6), injury to the recurrent laryngeal nerve (19.0%, n=4), subcutaneous emphysema (19.0%, n=4), chylothorax (9.5%, n=2), and subcutaneous hematoma (9.5%, n=2). There were three deaths, constituting 1.0% of cases, all of which were unrelated to surgery.

Table 1. Participants' characteristics (n=290)

Variable		Count	( %)
Age (Years)	Neonate (≤ 4 weeks)	49	(16.9)
	Infant (5 weeks to 1 year)	190	(65.5)
	Child (1-12 years)	51	(17.6)
Gender	Male	100	(34.5)
	Female	190	(65.5)
Type of Intervention	PDA simple ligation	47	(16.2)
	PDA ligation with hemoclip application	238	(82.1)
	PDA ligation with division	5	(1.7)
Pulmonary hypertension	Mild	113	(39.0)
	Moderate to severe	177	(61.0)
Extubating location	In ICU	228	(78.6)
	In OT	62	(21.4)
Stay in ICU	less than 12 hours	84	(29.0)
	more than 12 hours	206	(71.0)
Discharge day	On the 5th day or earlier	262	(90.3)
	After the 5th day	28	(9.7)
Post-operative complications	No	269	(92.8)
	Yes	21	(7.2)
Type of post-operative complications	Chylothorax	2	(9.5)
	Injury to recurrent laryngeal nerve	4	(19.0)
	Residual duct	6	(28.6)
	Subcutaneous emphysema	4	(19.0)
	Subcutaneous hematoma	2	(9.5)
	Death	3	(14.3)
Death prior to discharge	No	287	(99.0)
	Yes	3	(1.0)

The Association Between Participants’ Characteristics and their Length of ICU Stay

Table 2 shows the association between patients’ characteristics and their length of stay in the ICU, categorized as ≤12 hours and >12 hours. Extubation location was significantly associated with the length of stay in the ICU (χ2 = 159.860, p < 0.001). Patients extubated in the operating room experienced a shorter ICU duration compared to those extubated in the ICU. Additionally, post-operative complications were significantly associated with ICU stay duration (χ2 = 9.232, p = 0.002), indicating that patients with complications had a prolonged ICU stay. On the other hand, gender, age, type of PDA intervention, discharge day, and mortality before discharge did not exhibit a significant association with ICU stay duration (p > 0.05).

Table 2. Association between participant's characteristics and staying in the ICU

Variable		Stay in ICU				Chi-square	P value
		≤12 hours		> 12 hours
		Count	(%)	Count	(%)
Age	Neonate	12	(24.5)	37	(75.5)	2.744	0.254
	Infant	61	(32.1)	129	(67.9)
	Child	11	(21.6)	40	(78.4)
Gender	Male	28	(28.0)	72	(72.0)	0.069	0.793
	Female	56	(29.5)	134	(70.5)
Type of Intervention	PDA simple ligation	16	(34.0)	31	(66.0)	0.703	0.402
	PDA ligation with hemoclip application/division	68	(28.0)	175	(72.0)
Pulmonary hypertension	Mild	39	(34.5)	74	(65.5)	2.769	0.096
	Moderate	45	(25.4)	132	(74.6)
Extubating location	In OT	58	(93.5)	4	(6.5)	159.860	<0.001*
	In ICU	26	(11.4)	202	(88.6)
Discharge day	On the 5th day or earlier	80	(30.5)	182	(69.5)	3.246	0.072
	After the 5th days	4	(14.3)	24	(85.7)
Post-operative complications	No	84	(31.2)	185	(68.8)	9.232	0.002*
	Yes	0	(0.0)	21	(100.0)
Death prior to discharge	No	84	(29.3)	203	(70.7)	1.236	0.559a
	Yes	0	(0.0)	3	(100.0)

Abbreviation: OT: Operating Theater; ICU: Intensive Care Units; PDA: Patent Ductus Arteriosus; a: Fisher’s exact test was used.

Association Between Participants' Characteristics and Their length of Hospital stay

The relationship between participants’ characteristics and the duration of hospitalization is shown in Table 3. Pulmonary hypertension showed a significant association with length of hospital stay (χ² = 5.806, P = 0.016). Patients with moderate to severe pulmonary hypertension had a greater likelihood of prolonged hospitalization. Additionally, post-operative complications were significantly associated with the length of hospital stay (χ² =190.09, P < 0.001). Patients who experienced post-operative complications were significantly more likely to require hospitalization for more than 5 days. Conversely, gender, age, extubating location, and type of surgical intervention did not exhibit a significant association with length of hospital stay (P > 0.05).

Table 3. Association between participant's characteristics and hospitalization stay

Variable		Discharge day				Chi-square	P value
		On the 5th day or earlier		After the 5th day
		Count	(%)	Count	(%)
Age	Neonate	43	(87.8)	6	(14.3)	0.683	0.735a
	Infant	173	(91.1)	17	(8.4)
	Child	46	(90.2)	5	(9.8)
Gender	Male	92	(92.0)	8	(8.0)	0.479	0.489
	Female	170	(89.5)	20	(10.5)
Type of Intervention	PDA simple ligation	45	(95.7)	2	(4.3)	1.875	0.278a
	PDA ligation with hemoclip application/division	217	(89.3)	26	(10.7)
Pulmonary hypertension	Mild	108	(95.6)	5	(4.4)	5.806	0.016*
	Moderate to severe	154	(87.0)	23	(13.0)
Extubating location	In ICU	202	(88.6)	26	(11.4)	3.737	0.053
	In OT	60	(96.8)	2	(3.2)
Post-operative complications	No	261	(97.0)	8	(3.0)	190.09	<0.001*,a
	Yes	1	(4.8)	20	(95.2)

Abbreviation: OT: Operating Theater; ICU: Intensive Care Units; PDA: Patent Ductus Arteriosus; a: Fisher’s exact test was used.

Associations between participants' characteristics and the extubation location

Table 4 reveals significant associations between participants' characteristics and the extubation location, either in the operating theater or ICU. Pulmonary hypertension severity exhibited a significant association with extubation location (χ2 = 19.410, P < 0.001). Patients with moderate to severe pulmonary hypertension were more likely to be extubated in the ICU, while those with mild pulmonary hypertension were more likely to be extubated in the operating theater. On the other hand, age, gender, type of intervention, and postoperative complications did not show significant associations with extubation location.

Table 4. Association between participant's characteristics and extubating location

		Extubating location				Chi-square	P value
		In OT		In ICU
		Count	(%)	Count	(%)
Age	Neonate	9	(18.4)	40	(81.6)	1.848	0.397
	Infant	45	(23.7)	145	(76.3)
	Child	8	(15.7)	43	(84.3)
Gender	Male	16	(16.0)	84	(84.0)	2.628	0.105
	Female	46	(24.2)	144	(75.8)
Type of Intervention	PDA simple ligation	11	(23.4)	36	(76.6)	0.137	0.711
	PDA ligation with hemoclip application/division	51	(21.0)	192	(79.0)
Pulmonary hypertension	Mild	39	(34.5)	74	(65.5)	19.000	<0.001*
	Moderate to severe	23	(13.0)	154	(87.0)
Post-operative complications	No	60	(22.3)	209	(77.7)	1.893	0.169a
	Yes	2	(9.5)	19	(90.5)

Abbreviation: OT: Operating Theater; ICU: Intensive Care Units; PDA: Patent Ductus Arteriosus; a: Fisher’s exact test was used.

Association between participant characteristics and postoperative complications

Table 5 provides insights into the association between participant characteristics and the occurrence of postoperative complications. Pulmonary hypertension demonstrated a significant association with occurrence of postoperative complications (χ^2 = 5.798, p = 0.016). Patients with moderate to severe pulmonary hypertension were more likely to develop postoperative complications compared with mild pulmonary hypertension. On the other hand, age, gender, and type of intervention did not significantly impact postoperative complications.

Table 5. Association between participant's characteristics and post-operative complications

		Post-operative complications				Chi-square	P value
		No		Yes
		Count	(%)	Count	(%)
Age	Neonate (≤ 4 weeks)	46	(93.9)	3	(6.1)	0.755	0.752a
	Infant (5 weeks to 1 year)	177	(93.2)	13	(6.8)
	Child (1-12 years)	46	(90.2)	5	(9.8)
Gender	Male	95	(95.0)	5	(5.0)	1.142	0.285
	Female	174	(91.6)	16	(8.4)
Type of Intervention	PDA simple ligation	46	(97.9)	1	(2.1)	3.644	0.142a
	PDA ligation with hemoclip application/division	223	(91.8)	20	(8.2)
Pulmonary hypertension	Mild	110	(97.3)	3	(2.7)	5.798	0.016*
	Moderate to severe	159	(89.8)	18	(10.2)

Abbreviation: OT: Operating Theater; ICU: Intensive Care Units; PDA: Patent Ductus Arteriosus; b: Fisher’s exact test was used.

DISCUSSION

This study conducted over the period from May 2017 to May 2022, revealed noteworthy findings regarding patients undergoing PDA closure in a cardiac center in Yemen. Although all patients attending to cardiac centers had pulmonary hypertension with a different severity level, those who have moderate to severe pulmonary hypertension experienced longer stays in both ICU and in the hospital. Additionally, they demonstrated postoperative complications and had a lower likelihood of being extubated in the operating room. Furthermore, patients with postoperative complications were more likely to stay in the ICU longer than those without complications.

In the current study, the majority of patients who underwent PDA closure were female. This observation aligns with recent research conducted in the United States, which found that PDA is twice as common among females compared with male [25]. Furthermore, a female predominance was noted in cases of PDA and coarctation of the aorta, reinforcing the observed demographic trend in our study [21,26].

This study showed that patients with mild pulmonary hypertension tend to spend a shorter duration in the ICU compared to those with moderate to severe pulmonary hypertension. This might be interpreted as that the patients with mild pulmonary hypertension are clinically stable and less likely to develop pulmonary hypertension-related complications in this stage. Therefore, they are likely to stay shorter in the ICU compared to patients with moderate to severe pulmonary hypertension. Aligning with our findings, a study conducted in China among preterm infants, which emphasized the importance of pulmonary hypertension severity on patient outcomes [27].

A significant association between postoperative complications and the severity of pulmonary hypertension aligns with prior research by Lammers et al., highlighting increased symptom severity and mortality risks in patients with pulmonary hypertension [28].

 The correlation between delayed presentation and complications has also been identified in studies in a developing country. This delay significantly complicates the management of congenital heart disease [29,30]. A previous study has shown that performing surgical ligation of the PDA in preterm infants three weeks earlier results in more favorable outcomes in nutrition and ventilation compared to delaying PDA closure by three weeks. This delay can lead to pulmonary overcirculation and alveolar edema, compromising pulmonary function [31]. In Yemen, delayed presentation of PDA is likely to be attributed to patients-related socioeconomic factors and healthcare system-related factors. Primarily as a result of the ongoing war and political instability. The delay in seeking healthcare service in Yemen is not unique to PDA patients. A study has shown that 72% of patients with ST-elevation acute myocardial infarction in Yemen are admitted too late, impacting mortality rates compared to the Western hemisphere [32]. Therefore, addressing the causes of delayed presentation is crucial for improving outcomes associated with PDA closure.

This study also showed that patients with mild pulmonary hypertension were more likely to be extubated in the operating room compared to those with moderate to severe pulmonary hypertension. This interpretation hinges on the assumption that patients with mild pulmonary hypertension are less likely to have structural lung damage, unlike their counterparts with moderate to severe cases. Previous research has emphasized the role of chronic lung disease development in determining the timing of extubation after PDA closure [33].

The current study showed that patients who had shorter ICU stay were more likely to be extubated early in the operating room. This finding is consistent with the results of a recent Turkish study that investigated extubation strategies in patients with congenital heart disease. It demonstrated a significant correlation between reduced duration of ICU stay and the extubation strategy [34].

There are many different treatment approaches for PDA in premature neonates. While it is acceptable to simply ligate or hemoclip PDA in preterm infants, in older patients, a more comprehensive approach involving double or triple ligation, as well as division and oversewing, is recommended to reduce the risk of incomplete closure or recanalization [25]. In the current study, no significant association was observed between the method of PDA closure (simple ligation or PDA ligation with hemoclip application/division) with the measured outcomes, such as length of stay in the ICU and hospital, extubation and postoperative complications, emphasizing the safety of these techniques for PDA closure. The findings of this study are in agreement with recent studies endorsing surgical ligation and transcatheter occlusion as effective and comparable closure modalities, despite potential variations in hospital stays [35,36].

Complications were observed in 9.7% of patients, with residual duct, recurrent laryngeal nerve injury, and subcutaneous emphysema being the most common issues. Similar findings were observed from previous studies elsewhere [36-38]. Mortality in the current study aligns with that reported in the study by Zulqarnain and his colleagues [37]. Another study in a developing country reported 4% as the 30-day post-operative mortality rate for congenital heart disease [29]. It's worth mentioning that the mortality assessed in our study is limited to in-hospital mortality and is not directly associated with the surgical procedure.

Study limitation

This retrospective study design introduces the potential for recall bias, given its reliance on past data and patient recollections. Additionally, this study focusses only on the short-term complication of the PDA closure without considering the longer-term surgical complications. Furthermore, the evaluation of pulmonary hypertension based on echocardiographic measurements presents limitations, including the risk of misinterpreting postcapillary pulmonary hypertension as pulmonary arterial hypertension. Nevertheless, previous research has indicated an acceptable level of accuracy for transthoracic echocardiography when compared to invasive assessments [39].

CONCLUSION

In patients with PDA, timely closure of PDA is pivotal in preventing pulmonary and cardiac complications. Although trans catheter closure has been associated with lower adverse outcomes, surgical closure continues to serve as the gold standard approach, particularly in resource-limited settings. Pulmonary hypertension has impact on the treatment outcomes, including length of hospital stay, extubation location, and the development of postoperative complications. Therefore, early detection and management of PDA is vital to prevent the development of complications. The establishments of a health network that facilitates smooth referrals from primary healthcare units to surgical centers can help achieve this goal. Further research is warranted to explore long-term outcomes and the suitability of specific techniques for different patient populations. Importantly, our study highlights those various surgical techniques yield favorable outcomes, with no significant differences observed in terms of ICU length of stay, overall hospital stays, extubation from ventilation, and postsurgical complications.

FUNDING

No funding was received for conducting this study.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

ETHICAL CONSIDERATIONS

Scientific and administrative approvals were obtained from the Yemeni Council for Medical Specialization, Ministry of Public Health and Population, and Al-Thawra Modern General Hospital prior to conducting the study. Patient names and personal information were kept confidential and solely used for research purposes.

REFERENCES

1. Brown ER. (1979). Increased risk of bronchopulmonary dysplasia in infants with patent ductus arteriosus. J Pediatr. 95(5 Pt 2):865-866.
2. Mirza H, Garcia J, McKinley G, Hubbard L, Sensing W, Schneider J, et al. (2019). Duration of significant patent ductus arteriosus and bronchopulmonary dysplasia in extremely preterm infants. J Perinatol. 39(12):1648-1655.
3. Noori S, McCoy M, Friedlich P, Bright B, Gottipati V, Seri I, et al. (2009). Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics. 123(1):e138-e144.
4. Laughon MM, Simmons MA, Bose CL. (2004). Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated? Curr Opin Pediatr. 16(2):146-151.
5. Dice JE, Bhatia J. (2007). Patent ductus arteriosus: an overview. J Pediatr Pharmacol Ther. 12(3):138-146.
6. Liu C, Zhu X, Li D, Shi Y. (2020). Related Factors of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis. Frontiers in pediatrics. 8:605879.
7. Benitz WE. (2012). Patent ductus arteriosus: to treat or not to treat? Arch Dis Child Fetal Neonatal Ed. 97(2):F80-F82.
8. Ulrich TJB, Hansen TP, Reid KJ, Bingler MA, Olsen SL. (2018). Post-ligation cardiac syndrome is associated with increased morbidity in preterm infants. J Perinatol. 38(5):537-542.
9. Schräder R, Kadel C. (1993). Persistierender Ductus arteriosus--ist auch bei asymptomatischen Erwachsenen mit kleinem Ductus und geringem Shunt ein Verschluss indiziert? [Persistent ductus arteriosus--is closure indicated also in asymptomatic adults with small ductus and minor shunt?]. Z Kardiol. 82(9):563-567.
10. Stącel T, Sybila P, Mędrala A, Ochman M, Latos M, Zawadzki F, Pióro A, et al. (2022). Novel Hybrid Treatment for Pulmonary Arterial Hypertension with or without Eisenmenger Syndrome: Double Lung Transplantation with Simultaneous Endovascular or Classic Surgical Closure of the Patent Ductus Arteriosus (PDA). J Cardiovasc Dev Dis. 9(12):457.
11. Bhalgat PS, Pinto R, Dalvi BV. (2012). Transcatheter closure of large patent ductus arteriosus with severe pulmonary arterial hypertension: Short and intermediate term results. Ann Pediatr Cardiol. 5(2):135-140.
12. Mills NL, King TD. (1976). Nonoperative closure of left-to-right shunts. J Thorac Cardiovasc Surg. 72(3):371-378.
13. Saucedo-Orozco H, Vargas-Barrón J, Vázquez-Antona CA, Castillo-Castellón F. (2021). Echocardiographic findings in patent ductus arteriosus-associated infective endarteritis. Anatol J Cardiol. 25(11):774-780.
14. Henry BM, Hsieh WC, Sanna B, Vikse J, Taterra D, Tomaszewski KA. (2019). Incidence, Risk Factors, and Comorbidities of Vocal Cord Paralysis After Surgical Closure of a Patent Ductus Arteriosus: A Meta-analysis. Pediatr Cardiol. 40(1):116-125.
15. Benjamin JR, Smith PB, Cotten CM, Jaggers J, Goldstein RF, Malcolm WF. (2010). Long-term morbidities associated with vocal cord paralysis after surgical closure of a patent ductus arteriosus in extremely low birth weight infants. J Perinatol. 30(6):408-413.
16. Ulrich TJB, Hansen TP, Reid KJ, Bingler MA, Olsen SL. (2018). Post-ligation cardiac syndrome is associated with increased morbidity in preterm infants. J Perinatol. 38(5):537-542.
17. Ahmadi A, Sabri M, Bigdelian H, Dehghan B, Gharipour M. (2014). Comparison of cost-effectiveness and postoperative outcome of device closure and open surgery closure techniques for treatment of patent ductus arteriosus. ARYA Atheroscler. 10(1):37-40.
18. UN. United Nations Population Fund. (2023). World Population Dashboard Yemen 2023. Available from: https://www.unfpa.org/data/world-population/YE.
19. Al-Awlaqi S, Dureab F, Annuzaili D, Al-Dheeb N. (2020). COVID-19 in Conflict: The devastating impact of withdrawing humanitarian support on universal health coverage in Yemen. Public Health Pract (Oxf). 1:100015.
20. Al Waziza R, Sheikh R, Ahmed I, Al-Masbhi G, Dureab F. (2023). Analyzing Yemen's health system at the governorate level amid the ongoing conflict: a case of Al Hodeida governorate. Discov Health Syst. 2(1):15.
21. Al-Wather NA, Munibari AN. (2013). Pattern of congenital heart disease in the cardiac center of al-thawra general teaching hospital. J Saudi Heart Assoc. 25(2):157.
22. Yehya MTB, Hadi AA, Ba-Saddik IA. (2022). Pattern and Diagnosis of Congenital Heart Disease in Children Admitted to Al-Sadaqa Teaching Hospital, Aden, January 2017-December 2019. Yemeni Journal of Medical and Health Research. 11(1&2).
23. Badi MAH, Triana BEG. (2014). Congenital heart diseases in neonatal unit at Al-Wahda Pediatric Teaching Hospital, Aden, Yemen (2012-2013). Revista Habanera de Ciencias Médicas. 13(5):708-718.
24. Saleh HK. (2009). Pattern of congenital heart disease in Southern Yemeni children referred for echocardiography. Saudi Med J. 30(6):824-828.
25. Stephens EH, Tannous P, Backer CL, Mavroudis C, et al. (2023). Patent Arterial Duct. Pediatric Cardiac Surgery. p. 213-224.
26. Park YA, Kim NK, Park SJ, Yun BS, Choi JY, Sul JH. (2010). Clinical outcome of transcatheter closure of patent ductus arteriosus in small children weighing 10 kg or less. Korean J Pediatr. 53(12):1012-1017.
27. Deng Y, Zhang H, Zhao Z, Du J, Bai R, McNamara PJ. (2022). Impact of patent ductus arteriosus shunt size and duration on risk of death or severe respiratory morbidity in preterm infants born in China. Eur J Pediatr. 181(8):3131-3140.
28. Lammers AE, Bauer LJ, Diller GP, Helm PC, Abdul-Khaliq H, Bauer UMM, Baumgartner H; German Competence Network for Congenital Heart Defects Investigators. (2020). Pulmonary hypertension after shunt closure in patients with simple congenital heart defects. Int J Cardiol. 308:28-32.
29. Mocumbi AO, Lameira E, Yaksh A, Paul L, Ferreira MB, Sidi D. (2011). Challenges on the management of congenital heart disease in developing countries. Int J Cardiol. 148(3):285-288.
30. Phuc VM, Tin do N, Giang do TC. (2015). Challenges in the management of congenital heart disease in Vietnam: A single center experience. Ann Pediatr Cardiol. 8(1):44-46.
31. Ibrahim MH, Azab AA, Kamal NM, Salama MA, Elshorbagy HH, Abdallah EAA, et al. (2015). Outcomes of Early Ligation of Patent Ductus Arteriosus in Preterms, Multicenter Experience. Medicine (Baltimore). 94(25):e915.
32. Munibari AN, Al-Motarreb A, Alansi A, Cimino S, La Torre G, Agati L. (2015). Reperfusion therapy for ST elevation acute myocardial infarction in Yemen: Description of the current situation: Data from Gulf Registry of Acute Coronary Events (the Gulf RACE-I). Int J Cardiol. 187:128-129.
33. Clyman RI. (2018). Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity. Semin Perinatol. 42(4):235-242.
34. Biçer M, Kozan Ş, Darçın K, Çetin S, Tanyıldız M, Kızılkaya M, et al. (2023). Predictors of extubation in the operating room after pediatric cardiac surgery: A single-center retrospective study. Turk Gogus Kalp Damar Cerrahisi Derg. 31(4):446-453.
35. Tabb C Jr, Aggarwal S, Bajaj M, Natarajan G. (2023). Comparative Effectiveness of Surgical Ligation and Catheter Closure of Patent Ductus Arteriosus in Preterm Infants. Pediatr Cardiol. DOI: 10.1007/s00246-023-03199-6.
36. Tort M, Ceviz M, Sevil F, Becit N. (2021). Surgical Treatment for Patent Ductus Arteriosus: Our Experience of 12 Years. Cureus. 13(4):e14731.
37. Zulqarnain A, Younas M, Waqar T, Beg A, Asma T, Baig MA. (2016). Comparison of effectiveness and cost of patent ductus arteriosus device occlusion versus surgical ligation of patent ductus arteriosus. Pak J Med Sci. 32(4):974-977.
38. Clement WA, El-Hakim H, Phillipos EZ, Coté JJ. (2008). Unilateral vocal cord paralysis following patent ductus arteriosus ligation in extremely low-birth-weight infants. Arch Otolaryngol Head Neck Surg. 134(1):28-33.
39. D'Alto M, Romeo E, Argiento P, D'Andrea A, Vanderpool R, Correra A. (2013). Accuracy and precision of echocardiography versus right heart catheterization for the assessment of pulmonary hypertension. Int J Cardiol. 168(4):4058-4062.