Transient left ventricular function deterioration after patent ductus arteriosus closure: A case series

Abstract

There is growing evidence of left ventricular decompensation following the closure of the patent ductus arteriosus, which most often happens early in the post-surgical time and improves on its own a few months after. Here, we aim to present nine cases whose left ventricular ejection fraction deteriorated early or late after the procedure. There were nine patients diagnosed with patent ductus arteriosus by echocardiography. The patients presented with a murmur, easy fatigability, exercise intolerance, and poor weight gain. The age varied from 5 months to 41 years old. Patients developed left ventricular ejection fraction deterioration, starting from the day after the operation to 3 years after the closure. Pre-closure left ventricular ejection fraction ranged from 60% to 75% and post-closure from 33% to 59%. The range for shortening fraction (SF) was from 30% to 42% and 16% to 31%, respectively. The patent ductus arteriosus was moderate to large in all patients. One patient was finally diagnosed with dilated cardiomyopathy. Patients with patent ductus arteriosus show left ventricular ejection fraction deterioration up to years after closure, whether percutaneous or operative. Large patent ductus arteriosus is associated with more complications and reduced post-surgery cardiac function due to the amount of the shunt before closure.

Background

Ductus arteriosus (DA), which originates from the sixth bronchial arch, connects the aorta and pulmonary artery.^1,2 Patent DA (PDA) is when the ductus remains open persistently. It is among the most common congenital heart defects, with an incidence of 0.3–4/1000 live births. This condition is more prevalent in females.^1,3 PDA comprises 5%–10% of congenital heart diseases. ⁴ It might be isolated or associated with other congenital heart defects. ¹ It is believed that spontaneous closure of PDA is unlikely after the first year of life. ¹ Prominent left-to-right shunt through PDA may cause many complications, such as pulmonary overcirculation and signs of congestive heart failure, and atrial arrhythmias, in which closure of PDA is recommended. PDAs carry a risk for endocarditis, and large PDAs, due to the high amount of shunt, might cause heart failure, and pulmonary vascular obstructive diseases. Therefore, surgical/percutaneous ligation of the PDA is needed.^1–3

The closure of the PDA is performed through a percutaneous transcatheter or a surgical technique.^1,5 Transcatheter closure is the preferred choice in adults and pediatrics in the majority of cases. ² Nonsteroidal anti-inflammatory drugs are given to preterm infants with a symptomatic PDA. In older babies, device closure or open surgery to ligate the opening with clips or stitches (if the PDA is large and causes a considerable shunt) is performed. Amplatzer ductal occluder makes the transcatheter closure of large PDAs possible. ⁶ According to the literature, left ventricular (LV) function deteriorates after surgical or device closure of PDA. ³ The most common imaging modality to evaluate PDA and hemodynamics is echocardiography. ³ During the first 12 h after PDA ligation, there might be signs of cardiopulmonary decompensation due to vascular dysregulation and decreased LV function and preload. ² Echocardiography and catheterization indices can help to find those more susceptible to LV dysfunction after PDA closure.^2,6 The changes in LV performance usually normalize after 6 months post-PDA closure. ⁶ Studies show LV dilation, high PAP, and low LV ejection fraction (LVEF) pre-closure are associated with a higher risk of developing post-PDA closure systolic dysfunction.^7,8 In this case series, we aim to present nine patients with PDA whose LV function decreased early or late post-PDA closure.

Cases

During 13 years from 2009 to 2022, there were 635 PDA closures in our institute (surgical and angiographic). Among these, we detected nine patients. Of course, there are some cases with missed follow-up 1.4% of patients experienced decreased LV systolic function. The cases that were referred for PDA closure were 5 months to 41 years old. Size of the PDA was evaluated according to echo findings by the cardiologist (dilatation of LA and LV, signs of pulmonary hypertension (PH), comparison between the size of PDA, and descending aorta (DAO), <1/3 DAO size considered as small, 1/3–2/3 DAO size moderate, and more than that large size) and intraoperative findings by the surgeon (comparing with patient’s subclavian artery). Some presented with decreased systolic function early post-closure (first month), and some late. Among all the cases, two patients presented with a decline in LVEF during the first 2 or 3 years after PDA closure (Table 1). We ruled out any myocardial pathology, including ischemic changes, before surgery according to the patients’ history, ECG, and echocardiography findings (such as abnormal dyskinesia). We follow the patients with echocardiography and ECG 1, 3, 6 months, and yearly after PDA closure if the patients did not complain of symptoms. In case of abnormal findings such as decreased LVEF, the intervals might change. Echocardiographic findings of the patients are reported in Table 1. All of the patients were evaluated and treated at the Chamran Hospital and the office of the pediatric cardiologists in Isfahan, Iran. Written consent was taken from the patients or their guardians before the study and confidentiality of data is emphasized. This case series is approved by the research ethics committee of Isfahan University of Medical Sciences (code: IR.ARI.MUI.REC.1402.242).

Table 1.

Demographics and echocardiographic findings of the patients with PDA.

Case number	Sex	Age (years)	Age at PDA closure	Time from closure to LVEF deterioration	Time needed for LVEF to normalize	Pre-closure EF (%)	Pre-closure FS (%)	Post-closure EF (%)	Post-closure FS (%)	AI	MR	PH	PDA size	Associated anomalies
1	Male	4.5	4 years	1 day	2 months	68	34	45	22	−	−	−	Moderate
2	Female	6.5	5.5 years	14 days	Missed follow-up	73	42	48	24	+/Mild	+/Mild	−	Moderate to large
3	Female	11	5 months	2.5 years	10 months	75	36	53	28	−	−	−	Moderate	−
4	Female	11.5	6 months	2 months	DCM	Not available	39	33	16	−	+/Mild	−	Moderate to large	DCMP
5	Female	12	7 years	1 day	1 year	73	36	46	22	+	+	−	Moderate
6	Female	13	6 months	3 years	2 years	Not available	Not available	59	31	−	−	−	Moderate
7	Female	25	18 years	1 day	20 months	68	34	53	27	−	−	−	Large
8	Female	42	35 years	20 days	10 months	68	34	52	27	+/Minimal	+/Minimal	−	Moderate to large	−
9	Female	48	41 years	1 day	13 months	60	30	50	25	−	+/Mild		Moderate	−

PDA: patent ductus arteriosus; LVEF: left ventricular ejection fraction; EF: ejection fraction; FS: fractional shortening; AI: aortic insufficiency; MR: mitral regurgitation; PH: pulmonary hypertension; DCMP: dilated cardiomyopathy; DCM: dilated cardiomyopathy.

Case 1

A 4-year-old boy was referred to the clinic due to a murmur. Moderate PDA was detected, and device closure was performed. The day after closure, the LVEF decreased for about 2 months. Digoxin was given during this period.

Case 2

A 5.5-year-old girl with poor weight gain was diagnosed as having moderate-to-large PDA, mild mitral regurgitation (MR), and aortic insufficiency (AI) in the evaluation, and PDA surgical closure was performed. LV function worsened about 2 weeks after closure, and the patient is on medication and follow-up.

Case 3

A 5-month-old girl was referred to the clinic due to a murmur. She had a continuous murmur and bounding pulse in the physical exam. A moderate-size PDA was seen on echocardiography, and surgical closure was decided. About 2.5 years after closure, a decline in LVEF was evident on echocardiography, the medication started, and the patient was followed routinely for nearly 9 years. The LV function went normal about 10 months later, and medications were tapered slowly.

Case 4

She presented to the clinic at the age of 6 months. PDA closure was performed surgically, and the patient had a decreased LVEF at follow-up 3 years after surgery. On the echocardiogram, a mild MR was reported. The patient was diagnosed with dilated cardiomyopathy (DCMP), and LVEF did not return to normal.

Case 5

A 7-year-old girl with a history of easy fatigability was referred to the clinic. On physical exam, continuous murmur and bounding pulse were detected, and moderate PDA with minimal MR and AI were confirmed on echocardiography. LVEF was decreased early after device closure and improved after 1 year.

Case 6

A 6-month-old girl was brought to the clinic due to a murmur found on the physical exam. A continuous murmur was detected, so echocardiography was requested, in which moderate PDA was found. After surgical PDA closure, LV function was normal for 3 years and then declined for about 2 years till improvement. Same as in the previous cases, the medications were given.

Case 7

An 18-year-old girl with exercise intolerance attended the clinic, and after evaluation, a large PDA was detected, and surgical closure was recommended. The LVEF started to decline the day after closure for about 20 months and then enhanced.

Case 8

A 35-year-old woman with a complaint of exercise intolerance and murmur was evaluated. On echocardiography, moderate-to-large PDA, minimal MR, and AI were detected, and the patient underwent surgical PDA closure. On the post-op echocardiogram, LV function was decreased, which took 10 months to improve. During that time, the patient received medications such as digoxin and captopril.

Case 9

A 40-year-old female presented with dyspnea. Moderate PDA and mild MR were detected on the conventional echocardiography, and the patient was referred to a surgeon. The day after PDA closure, the LVEF decreased and took 13 months to get normal. Captopril and digoxin were prescribed during the period and were tapered after improvement.

Discussion

Here, we reported nine cases with PDA, ranging in age from 5 months to 41 years old at the time of PDA closure. Pre-closure LVEF ranged from 60% to 75% and post-closure from 33% to 59%. The range for Shortening Fraction (SF) was from 30% to 42% and 16% to 31%, respectively. The patients mostly presented with a murmur in childhood, and adults mainly reported exercise intolerance and early fatigue. These symptoms warrant a need to perform an echocardiogram to evaluate for CHD requiring intervention. PDA patients presented with a decreased LVEF days to even years after surgical or device closure. All patients had isolated PDA. The mean time needed for LVEF to improve was 13 months. Consistent with the previous studies, most patients were female. ² Most patients lived in Isfahan city and its surrounding area at 1575 m altitude relative to the sea level. This affects the diameter of the ductus.^9,10 Our patients all had a moderate or large-diameter PDA.

Prolonged exposure to volume overload resulting from the left-to-right shunt due to a moderate-to-large PDA leads to muscle fibers getting stretched. Hemodynamic changes following the ligation, an increase in the afterload of LV, and a fall in the preload can lead to LV function deterioration.^11–14 There is a decrease in LV end-diastolic volume in these patients after the surgery. In around 8%–43% of the patients, LV dysfunction can be severe, and LVEF might fall below 55%. ⁷

A previous study showed the baseline systolic function to be related to post-transcatheter closure immediate systolic dysfunction. However, there were patients with normal LVEF at baseline who also had a decreased LVEF after the procedure. ⁸ Hemodynamic changes following PDA closure are more prominent in patients with a significant PDA in diameter. Our patients had a normal LVEF before closure, but most had a considerable-sized PDA.

In another study, 27 out of 191 pediatric PDA patients (14.1%) showed LVEF deterioration after 1 day of transcatheter closure. They showed pre-procedure LVEF to be an essential predictor of post-closure LV failure. They reported a cut-off of 66.5% for the pre-closure LVEF to predict early post-surgical LV dysfunction. It took 3 months for the LVEF to increase. ³ In the current study, the recovery time was higher, and one developed DCMP. One previous study showed that speckle-tracking echocardiography indices were reduced after PDA ligation. ⁴

In line with the previous reports, some patients might suffer from LV function deterioration long after the procedure.^15,16 Our patients presented with systolic dysfunction up to 3 years after the procedure. As seen in Table 1, we had two patients who were 5 and 6 months old at the time of the closure and showed LV dysfunction 2.5 and 3 years after the surgical repair of the PDA, respectively.

Another study in Ethiopia also showed that most of the patients were female. They showed the LVEF to deteriorate postoperatively from a mean of 65.06% to 54.83%. They showed that large-sized PDA and concurrent heart anomalies were associated with a higher risk for complications post-surgery. The fall in the LVEF and SF improved a few weeks after the procedure. ¹⁰ In our patients, it took longer for LVEF to normalize compared to this study.

We included pediatric and adult patients, and both showed considerable time needed for LVEF to get normal. Our patients all had a moderate-to-large diameter PDA, which might explain why the duration of cardiac decompensation was longer, and there was one patient diagnosed with DCMP thereafter. None of our patients demonstrated PH on the echocardiograms. However, AR or MR was present in five patients. Patients were followed for considerable years, and systolic performance was reserved except for one patient diagnosed with DCMP. All PDAs remained closed at follow-up.

Systolic decompensation after PDA ligation usually happens early after the surgery and recovers in a few weeks to months. ¹⁷ In the current study, we reported two patients with LV systolic dysfunction years after the surgery. In addition, the mean time from LVEF deterioration to LV performance normalization was about a year.

Limitations of the study

Here, we did not assess many cardiac function markers, and the indices measured on the conventional echocardiography are reported. We have mentioned the size of the PDA qualitatively, and it would be better to include the size in diameter. It was a case series study comprised of a few patients in a wide age range with the condition, and large-scale studies with long-term follow-up are needed to confirm the current results.

Conclusion

Although this rarely happens, patients with PDA might show LVEF deterioration up to years after ligation, whether percutaneous or operative. Patients may need cardiac supportive drugs such as digoxin, diuretics, and ACE inhibitors for a long time during LV decompensation after closure, as in our patients. This finding is more common in moderate-to-large PDAs due to the amount of the shunt before closure.