Clinical outcome in patients of atrial septal defects concurrent with severe pulmonary hypertension

doi:10.21203/rs.3.rs-4917758/v1

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Clinical outcome in patients of atrial septal defects concurrent with severe pulmonary hypertension

https://doi.org/10.21203/rs.3.rs-4917758/v1

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Objective

This study aims to retrospectively analyze the clinical outcomes of patients with atrial septal defects (ASDs) concurrent with severe pulmonary hypertension (pulmonary artery systolic pressure (PASP) ≥ 60 mmHg as measured by which estimated by echocardiography).

Methods

Clinical and examination data from a total of 229 patients with ASDs treated at our two hospitals from January 2018 to December 2023 were collected. Patients were categorized into a non-severe pulmonary hypertension group (189 patients) and a severe pulmonary hypertension group (40 patients) based on whether the PSAP was severe pulmonary hypertension or not. The clinical, surgery-related, and follow-up data between the two groups were compared to assess the clinical outcomes between the two groups. The primary endpoint event was death from cardiovascular complications, re-hospitalization due to heart failure, and arrhythmic complications. Kaplan-Meier curve was used to analyze the primary endpoint event. The log-rank test was used to compare differences between the two groups. COX proportional hazards regression models was applied to analyze the risk factors for the primary endpoint event at postoperative follow-up, and receiver operating characteristic (ROC)curve was applied to analyze the PASP to assess the threshold for contraindications to ASD surgery.

Results

The severe pulmonary hypertension group had significantly higher rates of atrial arrhythmias, grade II tricuspid regurgitation, proportion of cardiac function ≥ III, and right atrial and right ventricular diameters compared to the non-severe pulmonary hypertension group. The duration of hospitalization for operated patients in the severe pulmonary hypertension group was longer than that of the non-severe pulmonary hypertension group (P < 0.05). A total of 69 cases across both groups had primary endpoint event. There were 27 cases in the severe pulmonary hypertension group, including 4 deaths, and 42 cases in the non-severe pulmonary hypertension group, including 1 death. Kaplan-Meier curves showed a statistically significant difference (HR = 1.93, 95% CI, 1.11–1.32, P < 0.01), and Cox proportional hazards regression models analysis showed that severe pulmonary hypertension was an independent risk factor for the primary endpoint event in patients with ASD (HR = 2.3, 95% CI, 1.04–5.06, P < 0.01). The threshold for PASP to assess contraindications to surgery for ASD using ROC curve analysis was 65.5 mm Hg.

Conclusion

Our study confirms that ASD concurrent with severe pulmonary hypertension (≥ 60 mmHg) have an incidence of comorbidities and primary endpoint events. Reducing pulmonary artery pressure followed by occlusion or surgical repair can lead to better clinical outcomes. However, severe pulmonary hypertension must be avoided. A PASP of 65.5 mmHg may serve as a threshold for contraindication to surgery. Large prospective studies are required to validate this study’s findings.

Health sciences/Cardiology

Health sciences/Diseases

atrial septal defect

pulmonary hypertension

pulmonary artery systolic pressure

echocardiography

Atrial septal defect (ASD) is one of the most common congenital heart defects, accounting for 25–30% of all congenital heart diseases in adults [1]. Secundum ASD is the most common subtype in both adults and children, with an incidence of approximately 10.3 cases per 10,000 births [2]. Approximately 6–35% of secundum ASD cases are associated with pulmonary hypertension [3]. The incidence of pulmonary hypertension in untreated ASD adults ranges from 29–73%, whereas it varies between 5% and 50% following transcatheter closure [4]. Pulmonary hypertension increases mortality in congenital heart diseases [3], especially in elderly patients undergoing ASD transcatheter closure, where it is an independent mortality factor [5]. Consequently, cardiac surgeons have increasingly focused on it.

In childhood, ASD are typically asymptomatic, whereas in adulthood they are often associated with atrial arrhythmias, heart failure, and pulmonary hypertension [6]. Surgical intervention is necessary for: ASD symptomatic patients; patients with defects greater than 5 mm accompanied by right atrial ventricular enlargement (with or without symptoms); and patients with foramen ovale accompanied by headache symptoms [7]. The standard treatment for ASDs is surgical repair under extracorporeal circulation [8]. However, transcatheter closure is becoming the preferred treatment method due to its high success rate, reduced invasiveness, and improved cosmetic outcomes; these good outcomes are due to the use of minimally invasive techniques and the development of various occluders to treat ASDs [9–10]. Literature reports indicate that transcatheter ASD occlusion reduces pulmonary hypertension, improve cardiac function, decrease arrhythmias incidence [11–12], and benefit patients with concurrent pulmonary hypertension from ASD closure [13]. However, exacerbated pulmonary artery pressures may occur in some patients post-ASD occlusion [14–15]. Consequently, definitive indications for surgical treatment of ASD patients with pulmonary hypertension remain controversial [16].

Currently, treating patients with ASD combined with severe pulmonary hypertension is challenging due to lack of reliable research data [17, 18]. Right heart catheterization remains the gold standard for assessing hemodynamic parameters in patients with pulmonary hypertension. However, obtaining pulmonary flow/systemic flow(Qp/Qs) and pulmonary vascular resistance (PVR) is challenging and requires complex calculations [13, 19]. Some researchers recommended mean pulmonary artery pressure (MPAP) to determine surgical indications for ASDs with concurrent pulmonary hypertension [16]. There is lack of large-scale data on catheterization closure and surgical repair of ASD in cases of severe pulmonary hypertension (pulmonary artery systolic pressure (PASP) ≥ 60 mmHg). Therefore, this article analyzes clinical outcomes of comprehensive treatment in patients with ASDs and pulmonary artery systolic pressure ≥ 60 mmHg, providing a reference for the treatment of patients with ASDs with concurrent severe pulmonary hypertension.

2.1 Patient selection

Clinical and examination data of patients with ASDs treated at our hospital from January 2018 to December 2023 were collected and retrospectively analyzed. Inclusion criteria were: (1) patients diagnosed with secondary ASD; (2) patients who underwent either catheterization closure or intraoperative device closure, and surgical repair; and (3) patients who completed echocardiography both preoperatively and postoperatively. Exclusion criteria were: (1) infants and children with ASD but under 3 years old; (2) patients with other congenital cardiac anomalies; (3) patients with primary ASDs; and (4) patients with pulmonary artery embolism or other conditions that could lead to pulmonary hypertension.The study was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and People’s Hospital of Kizilsu Kirgiz Autonomous Prefecture, all methods were performed in accordance with the relevant guidelines and regulations .

2.2 Study groups

A retrospective research method was used. Based on echocardiography estimation of PSAP, patients were categorized into non-severe pulmonary hypertension group (PSAP < 60 mmHg, 189 patients) and severe pulmonary hypertension group (PSAP ≥ 60, 40 patients). Clinical data were collected from both groups, with follow-up starting upon discharge of the patients from hospital. Primary clinical outcomes such as death from cardiovascular causes and rehospitalization due to heart failure and arrhythmia were observed. Follow-up was performed by reviewing patients' hospitalization data or by telephone interviews, with the most recent examination results recorded.

2.3 Echocardiographic estimation of pulmonary artery systolic pressure

Pulmonary artery systolic pressure was calculated using tricuspid regurgitation velocity (V) and the Bernoulli Eq. (4V2 + right atrial pressure) [20]. Right atrial pressure was estimated from the diameter of the inferior vena cava, whereas the degree of inspiratory collapse of the inferior vena cava was measured using echocardiography. An inferior vena cava diameter < 2.1 cm and an inspiratory collapse > 50% resulted in a normal right atrial pressure of 3 mmHg, whereas an inferior vena cava diameter > 2.1 cm and an inspiratory collapse < 50% resulted in a right atrial pressure of 15 mmHg. In other cases, right atrial pressure was estimated at 8 mmHg [21].

2.4 Surgical procedure

2.4.1 ASD occluder device

Under local anesthesia, ASD occlusion was conducted using X-ray fluoroscopy and Trans Thoracic Echocardiography (TTE) guidance. The femoral vein was punctured, and a sheath was inserted. A guidewire and catheter were advanced through the ASD, and after exchanging the guidewire for a rigid one, the diameter of the ASD was measured using cardiac ultrasound. An occluder device (Shanghai Shape Memory Alloy Material Co. Ltd., Shanghai, China; Beijing Huamedicine&Shengjie Co. Ltd., Beijing, China) that was 4–6 mm larger than the diameter of the ASD was selected. A 7-12F delivery sheath tube was selected; it was advanced to the left atrium along the ultrarigid guidewire. The occlude device was then introduced and gradually released under fluoroscopic monitoring. After, a push-pull test was performed to check the occlude device stability, its position and shape were determined appropriate. It was then released. Postoperatively, the patients were prescribed oral aspirin of 100 mg per day and an antiplatelet therapy for six months.

2.4.2 Intraoperative device closure

Intraoperative device closure was used for patients unsuitable for transcatheter ASD occlusion. Under general anesthesia, the patient was placed in a supine position with the right chest elevated by 30, and then TEE was applied intraoperatively to assess the morphology and size of the ASD in comparison to the cardiac peripheral structures. A right anterolateral thoracic incision of approximately 3.0 cm was made, the pericardium was incised and sutured to suspend it, and heparin (1 mg/kg) was administered intravenously. The right atrium was sutured with a “purse string” and punctured, then under echocardiographic guidance, the guidewire was passed through the defect septum to the left atrium. The guidewrire was exchanged for a stiff one then the delivery sheath was advanced to the left atrium. An occluder device 4–6 mm larger than the diameter of the ASD was selected. It was introduced and gradually released after its stability was confirmed using the “push-pull” test. Postoperatively, patients were prescribed oral aspirin of 100 mg per day and antiplatelet therapy for six months.

2.4.3 ASD surgical repair

Surgical repair was used for patients who were unsuitable for the occlude device. Under general anesthesia, ASD surgical repair was performed using a median chest incision, a right anterolateral chest incision, or thoracoscopically. These approaches require extracorporeal circulation involving the use of autologous pericardial patches or artificial patches.

2.5 Indications for surgery

In this study, surgical intervention was based on the 2020 European Society of Cardiology and European Respiratory Society Guidelines for Adult Congenital Heart Disease. Adult patients with pulmonary hypertension ASDs and having a pulmonary vascular resistance index (PVR) of < 5 Wood unit (WU)/m2 were considered as candidates for either the occluder or surgical repair treatment [22]. Additionally, based on the guidelines by the American Heart Association/American College of Cardiology 2018, ASD patients with a pulmonary artery pressures less than two-thirds of the aortic pressure and no significant left-to-right shunt were considered [17]. All patients suspected of severe pulmonary hypertension underwent right heart catheterization or pulmonary artery pressure monitoring to assess a necessity for surgical intervention.

2.6 Statistical methods

Measurements were expressed as mean ± standard deviation (X ± s) or median (interquartile range), M(Q3-Q1). Student’s t-test or Mann-Whitney rank-sum test was used to make comparisons between the two groups. Categorical data were expressed as [n(%)], and comparisons between the two groups made using the chi-square test or Fisher's exact test. Normality was examined using the Kolmogorov-Smirnov test. Comparisons of continuous variables between time points within groups were performed using the paired t-test. Survival curves were estimated by the Kaplan-Meier method, and comparisons between groups were made using the log-rank test. Cox proportional hazards regression models was used to analyze risk factors for the occurrence of the primary endpoint event at postoperative follow-up. Clinically significant variables, P < 0.05, in univariate analysis were included in the multivariate regression model, which was refined using backward stepwise Cox proportional hazards regression models. All statistical analyses used two-tailed test with P < 0.05 considered to be significant. ROC curves were use to analyze the critical values of pulmonary artery pressures – as measured by cardiac ultrasound – that could serve as contraindications for surgical intervention. Statistical analysis was performed and processed using SPSS 20.0 and Graphpad Prism 9.3.0.

3.1

Data from 229 patients with ASDs were collected. The patients consisted of 64 (27.9%) males and 165 (72.1%) females, aged 3–78 years, with a mean age of 31.4 ± 16.7 years. Among 189 cases in non-severe pulmonary hypertension group, 185 (97.9%) completed surgical treatment, whereas 30 (75%) out of the 40 cases in the severe pulmonary hypertension group completed surgical treatment. Baseline clinical characteristics of the two groups are shown in Table 1. The number of atrial arrhythmias, cardiac function greater than or equal to III, and pulmonary vasodilator therapy were significantly higher in the severe pulmonary hypertension group compared to the the non-severe pulmonary hypertension group (P < 0.05). No significant differences were observed in the two groups in terms of age, gender, body mass index (BMI) and brain natriuretic peptide (BNP) (P > 0.05). Additionally, there were no significant differences observed between the two groups in relation to echocardiographic data, the diameter of ASD, diameter of the left atrial, diameter of the left ventricular end-diastolic, and the left ventricular ejection fractions (LVEF) (P > 0.05). However, the number of TR G ≥ II, PASP, the pulmonary artery diameter, the right atrial diameter, and the right ventricular diameter in patients with severe pulmonary hypertension were significantly greater than that of the non-severe hypertension patients (P < 0.05). The duration of hospitalization was longer in the severe pulmonary hypertension group compared to the non-severe pulmonary hypertension group (P < 0.05). Cardiac catheterization data, mean pulmonary artery pressure, and PVR were significantly higher in the severe pulmonary hypertension group compared to the non-severe pulmonary hypertension group (P < 0.05).

Table 1

Comparison of baseline clinical characteristics between the two groups BMI, body mass index; ASD, atrial septal defect; TR, tricuspid regurgitation; GII, grade II; PASP, pulmonary arterial systolic pressure; PA, pulmonary artery; LVEF, left ventricular ejection fractions; BNP, brain natriuretic peptide; NYHA, New York Heart Association functional class; MPAP, mean pulmonary arterial pressure; PVR, pulmonary vascular resistance.
Variables	Non-severe pulmonary hypertension group(n = 189)	severe pulmonary hypertension group(n = 40)	T/χ2/Z value	P value
Age(‾X ± s,years)	30.77 ± 17.27	34.55 ± 13.28	-1.30	0.19
Sex(male/female n)	52/137	12/28	0.10	0.75
BMI(‾X ± s)	22.34 ± 3.14	23.32 ± 2.70	-1.84	0.07
atrial arrhythmia[n(%)]	30(15.9)	12(30)	4.39	0.03
NYHA functional Class ≥ III[n(%)]	55(29.1)	19(47.5)	5.11	0.02
BNP(‾X ± s pg/ml)	38.19 ± 26.17	41.45 ± 21.48	-7.37	0.46
Pulmonary Vasodilator Therapy[n(%)]	33(17.46)	32(80)	63.52	0.00
Echocardiographic data
ASD size(‾X ± s,mm)	16.28 ± 7.59	19.83 ± 11.02	-1.93	0.06
TR ≥ GII [n(%)]	28(14.81)	16(40)	13.49	0.00
PASP (‾X ± s,mmHg)	42.61 ± 9.48	68.40 ± 10.13	-15.44	0.00
PA diameter(‾X ± s,mm)	21.53 ± 4.46	29.15 ± 3.65	-10.09	0.00
LVEF(‾X ± s,%)	60.72 ± 4.18	59.60 ± 4.19	1.54	0.12
Left atrial diameter(‾X ± s,mm)	31.20 ± 5.32	32.70 ± 3.68	-1.70	0.09
Left ventricular diameter(‾X ± s, mm)	39.93 ± 5.70	41.60 ± 5.07	-1.71	0.08
Right atrial diameter(‾X ± s,mm)	37.72 ± 8.37	45.00 ± 11.52	-3.78	0.00
Right Ventricular Diameter(‾X ± s, mm)	26.68 ± 6.85	32.33 ± 6.87	-4.72	0.00
Surgery related data
Number of surgeries[n(%)]	189(100)	30(75)	43.60	0.00
ASD occluder procedure/surgical repair(n)	135/54	17/13	2.65	0.10
Duration of hospitalization(‾X ± s, days)	9.21 ± 3.57	13.37 ± 9.06	-2.48	0.02
Antiarrhytmic surgery [n(%)]	12(6.48)	4(13.33)	0.90	0.34
cardiac catheterisation related data
Number of completed[n(%)]	57(30.15)	39(97.5)	61.48	0.00
MPAP(‾X ± s,mmHg)	45.60 ± 5.16	60.49 ± 7.54	-11.55	0.00
PVR [M(Q3-Q1) WU]	3.0(2.5–3.7)	4.7(7.6–4.2)	6.75	0.00

3.2 Follow-up results of surgical patients in the severe pulmonary hypertension group.

In the severe pulmonary hypertension group, comprising 30 patients who underwent surgery, there were no deaths from baseline values to the last follow-up. PASP was significantly reduced compared to baseline values (68.40 ± 10.13 mmHg vs 56.88 ± 19.83 mmHg; P < 0.00). The percentage of patients with a PASP ≥ 60 mmHg decreased significantly (100% vs 13.33%, P < 0.05). There was no significant change in LVEF compared to the baseline (59.60 ± 4.19 vs 61.00 ± 3.72, P > 0.05). The proportion of patients with tricuspid regurgitation ≥ GII decreased (33.33% vs 10%,p < 0.05). Right atrial diameter decreased significantly compared to the baseline (41.93 ± 11.12 mm vs 38.77 ± 8.57 mm; P < 0.00). Right ventricular diameter decreased significantly compared to the baseline (31.07 ± 7.59 vs 29.10 ± 7.23, P < 0.05). The proportion of patients with atrial arrhythmias decreased significantly (26.67% vs 6.67%, P < 0.05). The proportion of patients with cardiac function ≥ class III was reduced (43.33% vs 13.33%, p < 0.05). The pulmonary artery diameter decreased compared to the baseline (28.7 ± 3.30 mmHg vs 25.93 ± 2.86 mmHg, P < 0.00). See Table 2 for the detailed changes in the values.

Table 2

Changes in baseline and last follow-up data in patients operated on in the severe pulmonary hypertension group PASP, pulmonary arterial systolic pressure; TR, tricuspid regurgitation; GII, grade II; LVEF, left ventricular ejection fractions; NYHA, New York Heart Association functional class; PA, pulmonary artery.
Variables	Baseline data	Last follow-up data	T value/χ2 value	P value
PASP(‾X ± s,mmHg)	68.40 ± 10.13	56.88 ± 19.83	5.73	0.00
PASP ≥ 60 mmHg, [n(%)]	30(100)	4(13.33)	45.88	0.00
TR ≥ GII [n(%)]	10(33.33)	3(10)	4.81	0.02
LVEF(‾X ± s,%)	59.60 ± 4.19	61.00 ± 3.72	-1.18	0.07
atrial arrhythmia[n(%)]	9(26.67)	2(6.67)	5.45	0.02
Right atrial diameter(‾X ± s,mm)	41.93 ± 11.12	38.77 ± 8.57	2.70	0.01
Right Ventricular Diameter(‾X ± s,mm)	31.07 ± 7.59	29.10 ± 7.23	2.20	0.03
NYHA functional Class ≥ III[n(%)]	13(43.33)	4(13.33)	6.64	0.01
PA diameter(‾X ± s,mm)	28.7 ± 3.30	25.93 ± 2.86	3.96	0.00

3.3 Follow-up results of surgical patients in the non-severe pulmonary hypertension group

In the non-severe pulmonary hypertension group, comprising 189 patients, there were no deaths from baseline values to the last follow-up. PASP was significantly reduced compared to the baseline (42.61 ± 9.48 mmHg vs. 33.30 ± 10.20 mmHg, P < 0.00). The percentage of patients with a PASP ≥ 40 mmHg was significantly decreased (62.43%) vs 23.28%, P < 0.05). There was no significant change in LVEF compared to the baseline (60.72 ± 4.18 vs ± 61.49 ± 3.80, P > 0.05). There was a decrease in the percentage of patients with tricuspid regurgitation ≥ GII (14.81% vs 6.34%, P < 0.05). There was a significant decrease in right atrial diameter compared to the baseline (37.72 ± 8.37 mm vs 33.63 ± 7.73 mm, P < 0.05). Right ventricular diameter significantly decreased compared to the baseline (26.68 ± 6.85 vs 22.57 ± 7.23, P < 0.05). The proportion of patients with atrial arrhythmias decreased significantly (15.87% vs 6.87%, P < 0.05). The proportion of patients with cardiac function ≥ III significantly decreased (29.10% vs11.11%,p < 0.05). The pulmonary artery diameter decreased compared to the baseline (21.53 ± 4.46 mmHg vs 20.79 ± 4.35 mmHg, P < 0.00). See Table 3 for the detailed changes in the values.

Table 3

Changes in baseline and last follow-up data in patients operated on in the non-severe pulmonary hypertension group PASP, pulmonary arterial systolic pressure; TR, tricuspid regurgitation; GII, grade II; LVEF, left ventricular ejection fractions; NYHA, New York Heart Association functional class; PA, pulmonary artery.
Variables	Baseline data	Last follow-up data	T value/χ2 value	P value
PASP(‾X ± s,mmHg)	42.61 ± 9.48	33.30 ± 10.20	12.86	0.00
PASP ≥ 40 mmHg, [n(%)]	115(62.43)	44(23.28)	54.72	0.00
TR ≥ GII [n(%)]	28(14.81)	12(6.34)	7.15	0.01
LVEF(‾X ± s,%)	60.72 ± 4.18	61.49 ± 3.80	-1.83	0.06
atrial arrhythmia[n(%)]	30(15.87)	13(6.87)	7.58	0.01
Right atrial diameter(‾X ± s,mm)	37.72 ± 8.37	33.63 ± 7.73	7.94	0.00
Right Ventricular Diameter(‾X ± s,mm)	26.68 ± 6.85	22.57 ± 7.23	9.09	0.00
NYHA functional Class ≥ III[n(%)]	55(29.10)	21(11.11)	19.03	0.00
PA diameter(‾X ± s,mm)	21.53 ± 4.46	20.79 ± 4.35	3.55	0.00

3.4 Follow-up results of patients in both groups

At a median follow-up of 20 (12-28.5) months, the primary endpoint event occurred in 69 cases across both groups. Endpoint events occurred in 27 cases in the severe pulmonary hypertension group with a median postoperative follow-up of 22 (16–36) months; and four deaths reported among non-operated patients. Endpoint events occurred in 42 cases in the non-severe pulmonary hypertension group with a median postoperative follow-up of 18 (12–24) months; and one death reported. The Kaplan-Meier curves showed a statistically significant difference in the incidence of endpoint events between the severe and non-severe pulmonary hypertension groups (HR = 1.93, 95% CI, 1.11–1.32,P < 0.01), as shown in Fig. 1.

3.5 Analysis of risk factors for the occurrence of endpoint events at follow-up in both groups of patients

At a median follow-up of 20 (12-28.5) months, the occurrence of endpoint event in the two groups was analyzed. The endpoint event was set as the dependent variable, and the relevant factors in the baseline data of the two groups were set as the independent variables. Univariate Cox proportional hazards regression models analysis was performed, followed by multifactorial Cox proportional hazards regression models analysis. The results showed that severe pulmonary hypertension was an independent risk factor for the occurrence of the endpoint event (HR = 2.3, 95% CI, 1.04–5.06, P < 0.01), as shown in Table 4.

Table 4

COX proportional hazards regression models analysis of risk factors for endpoint events in patients with ASDs
Variables	Univariate regression analysis		Multifactor regression analysis
Variables	HR(95%CI)	p value	HR(95%CI)	p value
Age	1.02(1.01–1.03)	0.01	1.00(0.98–1.02)	0.73
BMI	1.11(1.02–1.20)	0.01	1.00(0.88–1.12)	0.97
Pulmonary Vasodilator Therapy	2.28(1.41–3.69)	0.00	1.17(0.61–2.25)	0.63
atrial arrhythmia	1.82(1.05–3.17)	0.03	1.22(0.68–2.16)	0.49
TR ≥ GII	2.07(1.25–3.43)	0.00	1.18(0.64–2.17)	0.58
NYHA functional Class ≥ III	1.93(1.19–3.13)	0.01	1.28(0.75–2.20)	0.35
Right atrial diameter	1.03(1.01–1.05)	0.00	0.99(0.96–1.02)	0.75
Right Ventricular Diameter	1.04(1.01–1.07)	0.01	0.98(0.95–1.02)	0.52
Left atrial diameter	1.05(1.01–1.10)	0.02	0.98(0.92–1.05)	0.66
PA diameter	1.09(1.04–1.13)	0.00	1.05(0.99–1.11)	0.85
PASP	1.03(1.02–1.05)	0.00	1.04(1.01–1.07)	0.00
severe pulmonary hypertension	1.99(1.21–3.27)	0.01	2.30(1.04–5.06)	0.03
BMI, body mass index; TR, tricuspid regurgitation; GII, grade II; NYHA, New York Heart Association functional class; PA, pulmonary artery; PASP, pulmonary arterial systolic pressure.

3.6 ROC curve analysis of PASP to assess contraindications to surgery for ASDs

All patients were included in the ROC curve analysis. The threshold for echocardiographic estimation of pulmonary artery pressure as a contraindication to surgery was 65.5 mmHg with an area under the curve (AUC) of 0.99 (sensitivity = 1, specificity = 0.95), as shown in Fig. 2.

Atrial septal defects are the most common congenital heart disease. Untreated ASDs are associated with pulmonary hypertension [23], resulting in higher mortality in these patients [24]. Echocardiography is an important for preoperative screening, surgical evaluation, and postoperative follow-up. Pulmonary hypertension is defined as pulmonary artery pressure ≥ 40 mmHg or PASP ≥ 50 based on echocardiography measurement; the clinical outcomes of pulmonary hypertension have been extensively analyzed and reported in previous studies [16, 25, 26, 27]. Our study included patients with congenital heart disease treated at our two hospitals. This study focused on the clinical outcomes of patients with pulmonary artery pressure < 60 mmHg and ≥ 60 mmHg. Both operable and inoperable patients were included in the study because of the ongoing challenges and uncertainties surgeons face in determining the optimal treatment options for patients with ASD concurrent with pulmonary arterial hypertension ≥ 60 mmHg.

Comparison of baseline characteristics in our study revealed that the number of people with TR ≥ GII were significantly greater in severe pulmonary hypertension group than in the non-severe hypertension group. Similarly, pulmonary artery diameter, right atrial diameter, and right ventricular diameter were significantly greater in the severe pulmonary hypertension group compared to the non-severe hypertension group. Additionally, duration of hospitalization was longer for severe pulmonary hypertension group compared to the non-severe hypertension group. Follow-up results showed that PASP decreased in severe pulmonary hypertension group. The group also had reduced right atrial and right ventricular diameters. Additionally there was a significant decrease in the proportion of patients with TR ≥ GII, atrial arrhythmias, and cardiac function ≥ class III in the severe pulmonary hypertension group; and a decrease in pulmonary artery diameter than baseline; however, there was no significant change in LVEF. The non-severe pulmonary hypertension group experienced similar results as the severe pulmonary hypertension group. These results were in agreement with the results reported in the literature [16]. However, literature indicates that pulmonary hypertension does not improve after correction of ASDs [14, 28]. Additionally, patients who develop pulmonary hypertension post-ASD surgery have worse prognosis [29]. In our study, postoperative echocardiographic follow-up indicated that four patients in the severe pulmonary hypertension group had PASP exceeding 60 mmHg, whereas 44 patients in the non-severe pulmonary hypertension group had PASP exceeding 40 mmHg. These results indicated that pulmonary hypertension was not completely resolved, but there were no cases of increase in PASP as reported in previous literature [15]. The discrepancy may be due to our strict surgical indications, which requires more cases or longer follow-up for definitive conclusions.

For patients with concurrent pulmonary hypertension, treat-and-repair is a reasonable treatment approach to reduce complications and mortality [30–32]. This approach may reduce perioperative mortality and improve prognosis in patients with high pulmonary vascular resistance [33]. In our study, 32 patients in the severe pulmonary hypertension group received medications to reduce pulmonary artery pressure, with 8 subsequently converting from surgical contraindications to indications. In the non-severe pulmonary hypertension group, 33 received medications to reduce pulmonary artery pressure, with all transitioning from the severe pulmonary hypertension group to the non-severe pulmonary hypertension group, successfully undergoing surgery with no report of death or serious complications. These results are consistent with existing literature, and confirm the safety and effectiveness of this approach. Advancement in medications to lower pulmonary artery pressure in patients with congenital heart disease concurrent with pulmonary hypertension have been effective [34]. Our study predominatly used endothelin receptor antagonists and phosphodiesterase type 5 inhibitors to lower pulmonary artery pressure; with patients taking only one type of these medications. With the popularity of ASD occlusion, the treatment rate of ASD has increased significantly. However, ASD closure surgery by itself increases the risk of death in patients with concurrent pulmonary hypertension [3]. Thus the optimal treatment approach for ASD concurrent with pulmonary hypertension remains unknown and controversial [29, 35]. Based on the latest guidelines for the treatment of congenital heart disease, the recommended PVR for surgical or catheter-based intervention of ASD is < 5 WU [36]. For patients with PVR ≥ 5 WU, our guideline is to administer specific pulmonary artery pressure-lowering medications, reassess hemodynamics, and consider surgery if the PVR < 5 WU with a left-to-right shunt or catheterized interatrial septal occlusion. This criterion was strictly followed in our study, excluding patients undergoing pre-occlusion balloon tests or those using fenestrated devices for ASD closure. Although the use of fenestrated device appropriate interventions can reduce pulmonary arterial hypertension and improve the quality of life for patients with pulmonary arterial hypertension, there is no guideline or expert consensus on this treatment. Moreover, fenestrated device can be spontaneously closed, leading to disease progression. Thus, further research is necessary to evaluate the efficacy and safety of fenestrated devices.

Our findings suggest that ASD early diagnosis and treatment helps to prevent its development to severe pulmonary hypertension. Pulmonary hypertension can be treated through oral medication to reduce pulmonary artery pressure and surgery when surgical indications are met. We analyzed the ROC curve to show that the critical value of pulmonary artery pressure for contraindications to surgery measured using echocardiography is 65.5 mmHg, which serves as a reference for clinicians. For patients with pulmonary artery pressure greater than 65.5 mmHg, further cardiac catheterization is necessary to assess surgical indication.

Our study data is relatively comprehensive, including patients who underwent occlusion, surgical repair, and those considered inoperable. However, there are limitations of this study. This study is a retrospective analysis conducted across our two centers, with a small sample size, with loss of some patients during follow-up, potentially introducing bias in the analysis. Additionally, we did not perform right heart catheterization in all patients, which is challenging to implement on a consistent basis in clinical practice. Moreover, certain data, such as Qp/Qs ratios, were not obtained due to practical difficulties in our clinical setting. Also, patients undergoing pre-occlusion balloon test or those with fenestrated device closures for ASD were excluded from this study..

In conclusion, our study confirms that ASD concurrent with severe pulmonary hypertension (≥ 60 mmHg) have high incidence of comorbidities and primary endpoint events. Reduction of pulmonary artery pressure followed by occlusion or surgical repair can lead to better outcomes but severe pulmonary hypertension cases must be avoided. A PASP of 65.5 mmHg may serve as a threshold for contraindication to surgery. However, large prospective studies are necessary to validate our findings.

Competing interests:

The author(s) declare no competing interests.

Informed Consent Statement:

Informed consent was obtained from all subjects involved in the study .

Author Contribution

Zhenchun Ji, Changhui Yu, Liying Han,conception and design of the study.Zhenchun Ji, Changhui Yu,Baihetiya Saimi,data collection.Zhenchun Ji,Liying Han, Kadeerjiang Musha，retrieval of the literature, content contribution, and writing the paper;Zhenchun Ji,Changhui Yu, Liying Han , Haoyue Huang,and Zhenya Shen finalizing the manuscript. All authors contributed to the manuscript revision, read,and approved the submitted version. All authors have read and agreed to the published version of the manuscript.

Acknowledgement

I would like to express my sincere gratitude to Zhenya Shen,who provided valuable guidance and support throughout this research.I am also grateful to other authors ,who provided me with invaluable feedback and suggestions during the writing process.In addition,I would like to acknowledge the assistance of Department of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University,whose help and resources were instrumental in the completion of this article. Finally,I would like to express my appreciation to my family and my friends,who have been a source of encouragement and support throughout the academic journey.

Data Availability

The data that support the findings of this study are available from the first author upon reasonable request. [email protected]

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No competing interests reported.

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Clinical outcome in patients of atrial septal defects concurrent with severe pulmonary hypertension

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Abstract

Objective

Methods

Results

Conclusion

Figures

1. Introduction

2. Methods

2.1 Patient selection

2.2 Study groups

2.3 Echocardiographic estimation of pulmonary artery systolic pressure

2.4 Surgical procedure

2.4.1 ASD occluder device

2.4.2 Intraoperative device closure

2.4.3 ASD surgical repair

2.5 Indications for surgery

2.6 Statistical methods

3. Result

3.1

3.2 Follow-up results of surgical patients in the severe pulmonary hypertension group.

3.3 Follow-up results of surgical patients in the non-severe pulmonary hypertension group

3.4 Follow-up results of patients in both groups

3.6 ROC curve analysis of PASP to assess contraindications to surgery for ASDs

Discussion

Declarations

Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

Supplementary Files

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