ASD: Atrial Septal Defect; CHD: Congenital Heart Disease; GUCH: Grown-up Congenital Heart Disease; TTE: TRANS-Thoracic Echocardiography; TEE: Trans-Esophageal Echocardiography; NYHA: New York Heart Association; VSD: Ventricular Septal Defect; BMI: Body Mass Index; AF: Atrial Fibrillation; PAP: Pulmonary Artery Pressure; SAID: Non-Steroidal Anti Inflammatory Drugs; ARDS: Adult Respiratory Distress Syndrome; SVT: Supraventricular Tachycardia

Patients with congenital heart diseases, especially those with low mortality in childhood, are more frequently reaching adult age. Isolated Secundum type atrial septal defect (ASD) is the most common form of congenital heart disease presented in adulthood after bicuspid aortic valve and mitral valve prolapse [1,2]. Pediatric cardiac surgery is an important landmark in the history of patients with CHD, since, before its development less than 20% of these children could survive to adult age [3]. Now we know that the majority of deaths occur at this adult age is greater than that of children with CHD [4,5]. These (GUCH) patients need special attention in an adequate setting in order to manage their problems and subsequent events intrinsic to the heart defect and also regarding age related co-morbidities [6].

There are several reasons, why patients may present with uncorrected lesions: late diagnosis is always a possibility, particularly in the case of ASD and aortic coarctation, as it is often clinically silent. Also other cases knew the lesion, but still reluctant or worried about the surgery, or those who need re-operations after successful repair because of residual defects or complications [7]. The progression of this congenital defect to congestive cardiac failure follows the onset of pulmonary hypertension, arrhythmias, respiratory infections, and other cardiovascular disease. Hence, the defect is usually discovered when a patient presents with dyspnea or palpitations, or occasionally on routine medical examination [8,9].

The main indication for ASD closure is the presence of a significant shunt as evidenced by right heart volume overload with or without symptoms (exercise intolerance, fatigue, dyspnea, heart failure, paradoxical emboli, and arrhythmias) [10,11]. Surgical repair of ostium Secundum or sinus venosus ASD performed early in childhood without significant residual lesions could be considered effective surgery [12]. The closure of an ASD in an adult, even when there is a significant left to right short circuit, may be less than satisfactory, and there is still doubt if these patients will benefit from surgical closure of atrial septal defects [13-15].

The purpose of our study was to determine the value of surgical closure of atrial septal defects in adults and the prognosis of these patients in relation to age. Also the impact of sildenafil use in pulmonary hypertensive cases.

Retrospective study was carried out on 489 patients with age 18 to 65 years old who had undergone surgical repair of isolated secundum type ASD. The study was in 3 tertiary centers in developing countries, between 2010 to 2014 and was approved by ethical committee of the tertiary centers. All clinical data and investigations concerned for them were collected and analyzed pre and post-operative (clinical, demographic, radiographic, electrocardiographic, echocardiographic (TTE) and (TEE) if done. All data were collected from hospital files after the consent was taken from the patients and near relatives. Inclusion criteria: All cases ≥ 18 years (adult congenital heart disease), with isolated secondum ASD type. Patients with normal PAP and those with reversible PAP by its criteria. Also, cases with sever PAP who received Sildenafil preoperatively.

Exclusion criteria: patients below 18 years old, those with other associated congenital heart diseases or acquired heart diseases. Cases with other types of ASD e.g. sinus venosus defect, ostium primum defect or unroofed coronary sinus. Patients with irreversible pulmonary hypertension confirmed by right heart catheterization.

There were 318 women (65%) and 171 men (35%) (Mean age: 25.21 ± 10.106 years). The patients were divided into two groups, group I: from 18-40 years old and Group II: from 40-65 years old. The diagnosis was confirmed by trans-thoracic echocardiography (TTE). The use of trans-esophageal echocardiography (TEE) was established in poorly visualized cases with routine TTE. Pre-operative and post-operative follow up was established with consultant cardiologists. Coronary angiography was performed for all patients over 40 years of age at presentation. Right heart catheterization was performed in all cases with sever pulmonary hypertension (SPAP above 50 mmHg). Post-operative echocardiography was done for all cases before discharge and 12 months post-surgery.

Surgical procedure

All operations were performed on pump using heart lung machine with moderate hypothermia around 32°C. The chest was opened through a median sternotomy or right thoracotomy. After total cardiopulmonary bypass had been instituted, cold crystalloid cardioplegic solution (St Thomas’ Hospital formula) was given antegrade through the aortic root in 290 cases and Fibrillator was used in 199.

In our study the method used to close the defect depended on its size. 154 patients with an isolated ASD underwent direct suture closure. The remainder required patch closure (with autologous pericardium or bovine pericardial patch) with either single or double layers of continuous sutures using Prolene 5-0. After weaning off bypass they were shifted to post-operative care unit for follow up then to regular ward till discharge home. Clinical data as New York Heart Association (NYHA) functional class and echocardiographic follow up evaluations was performed for all patients at 12 months intervals, or as soon as either new symptoms appeared or the previous clinical state deteriorated. All patients were followed up for 1 year. We compared clinical data, functional capacity, rhythm status, and echocardiographic parameters of all patients before and after the operation in both groups.

Statistical analysis

All data were collected, organized and statistically analyzed using SPSS software statistical computer package version 13 (SPSS, Chicago, Illinois, USA). For quantitative data, the range, mean, and standard deviation were calculated. Correlation between variables was evaluated. Significance was adopted at P<0.05 for interpretation of results of tests of significance.

There were 489 patients, 318 women (65%) and 171 men (35%), who met the inclusion criteria made up the population for this study. Mean age was 25.21 ± 10.106 years, with a range of 18 to 65 years of age. At the time of clinical evaluation, all patients were non cyanotic at rest and during exercise. 53 patients did not have significant symptoms, they were accidentally discovered. Symptoms as exercise intolerance, dyspnea or easy fatigability were the most significant finding in our patients. (Table 1)

Table 1: Presentations of cases in both groups. *P value<0.05 significant, Ns = Non-Significant.

Pre-operative clinical status and presentations were variable within each group of cases, but showed no significant difference between both groups (Table 1).

Palpitation was found in 125 cases (42.8%) in group I and 105 cases (53.3%) in group II. normal cardiac rhythm was found in 259 patients (52.9%). Tachyarrhythmia causing palpitation was found in 230 patients (47.1%) in both groups. They were divided by ECG into 55 cases with supraventricular tachycardia and 175 cases with atrial fibrillation. In the post-operative follow up, there was significant reduction of cases to 73 cases 14.9% with remained AF in a rate ranging between 75-110 beat/min under control using B blocker. Syncope was happened in 21 cases, secondary to rapid atrial fibrillation and supraventricular tachycardia.

Regarding systemic congestive symptoms, there was no significant difference between both groups. They were found in 44 cases in group I and 42 cases in group II .18 patients were presented after paradoxical embolization causing stroke with 13 cases in group I and 9 cases in group II (Table 1).

In this study NYHA class II was 83 cases (28.4%) in group I and was 39 cases (19.8%) in group II. In group I NYHA class IV was 25 cases (8.6%) and in group II NYHA class IV was 42 cases (21.4 %). We noticed that, NYHA class III and IV were 27.9% and 21.4% respectively in group II of patient which were higher than the group I. There was significant correlation between NYHA class preoperatively and age of the patients as NYHA class preoperatively more higher in group II than group I (Table 2).

Table 2: Functional status (NYHA class) of patients pre-operatively and post operatively for both groups. *Significant (p<0.05).

NYHA class II, III and IV were significant finding in 122, 112 and 68 patients respectively preoperative in all cases (Table 3).

Table 3: Improvement in NYHA class post-operatively as a whole. *Significant (P<0.05).

Regarding the surgical incision used, 228 cases underwent median sternotomy in group I and 154 cases in group II. On the other hand 64 cases underwent thoracotomy in group I and 43 cases in group II (Table 4).

Table 4: The type of incision and use of cardioplegia.

In this study cardioplegia was given to185 cases in group I and to 105 cases in group II. Fibrillator was used to fibrillate the heart in 107 cases in group I and in 92 cases in group II. No significant surgical technical difference for those cases either sternotomy or thoracotomy or according to the method used to arrest the heart (Table 4). No residual intra-cardiac shunt was identified on echocardiographic follow up.

Overall patients were followed up for 1 year. There were significant improvement of NYHA functional class, tricuspid valve regurgitation and pulmonary artery pressure in most of the patients after operation with more improvement in group I than group II (Tables 2 and 3). Cases in our study with pre-operative tricuspid regurgitation showed significant improvement post-operatively in group I more than in group II (Figure 1). There was no tricuspid regurgitation in 118 cases (40.4%) post-operatively in group I and in 80 cases (40.6%) in group II (Table 5).

Figure 1: Improvement of degree of tricuspid valve regurgitation in both groups.

Table 5: Tricuspid valve regurgitation preoperative and postoperative. *Significant (p<0.05) improvement in tricuspid regurge.

On measuring PAP post- operatively, There was significant reduction of it to the mean 14.9 ± 14 mm Hg, (minimum pressure was 5 mmHg and maximum was 30 mmHg), from pre-operative mean PAP 55 ± 13 mmHg in group I. Also in the group II, Mean PAP pre-operatively was 43.23 mmHg (minimum pressure of 26 mmHg and the maximum pressure was 99 mmHg) and significantly declined to be post-operatively mean PAP was 23.9 ± 15 mmHg, (minimum pressure was 10 mmHg and the maximum pressure was 45 mmHg). Over all pulmonary artery pressure showed significant reduction in our cases post-operatively with group I more than in group II (Table 6).

Table 6: Pulmonary artery pressure by echocardiography. *Significant (p<0.05).

There was significant correlation between age of patients and hospital stay, as it was shorter in group I than the group II. In group II some complications occurred and these complications were the leading causes to prolong their hospital stay (Table 7).

Table 7: Post-operative data in the two groups of patients including mortality. *Significant (p<0.05).

Regarding the post-operative morbidities, there was significant correlation between age of patients and post-operative morbidities as wound infection, pericardial effusion and bleeding secondary to coagulopathy with higher occurrence of these complications in the group II of patients. The postoperative medical bleeding occurred in 7 cases (2.4%) in group I and in 31 cases (15.7%) in group II. The postoperative pericardial effusion occurred in 19 cases (6.5 %) in group I and 60 cases (30.4%) in group II the majority managed with diuretics, NSAID and follow up. The postoperative wound infection found in 13 cases (4.5%) in group I and 28 cases (14.2%) in group II. There was no significant difference between both groups regarding ICU stay and ventilation hours (Table 7).

Our study showed that, the mortality was documented in group I and II. There were 3 deaths in the series. First case was a 49 years old from group II female died intra-operatively most probably due to irreversible protamine hypersensitivity, the second case was a 33 years old male died at the 4^th post-operative day most probably due to ARDS, and the third post-operative death was a 65 years old male patient who died in the second post-operative day due to massive cerebrovascular accident (Table 7).

In our study, there was significant improvement in the quality of life as improvement of symptoms as dyspnea, palpitation physical activity and congestive manifestations (Figure 2). Also we can notice significant improvement post operatively in group I and II, but more in group I (Figure 3).

Figure 2: Improvement in NYHA class post-operatively.

Figure 3: Difference in NYHA class pre and post operatively in both groups of cases.

In this study, sildenafil therapy showed significant improvement of PAP postoperatively. Cases with significant pulmonary hypertension (SPAP above 50 mmHg) were 103 cases; they received sildenafil for 6 months preoperative. In group I about 53 cases had severe pulmonary hypertension and 51 cases in group II preoperatively. In the postoperative follow up there was high significant improvement in PAP in patients who received sildenafil in both groups, as only 4 cases in group II still had high PAP (Table 8).

Table 8: Post -operative PAP after the use of Sildenafil in 104 pulmonary hypertensive cases pre operatively.

There is no precise data about the group of grown-up congenital heart disease patients (GUCH) in the Middle East. This needs multicentre collaboration. In Middle East countries, these cases diagnosed late either due to lake of facilities or accidentally discovered recently with routine investigations. Also, certain cultures, still worry to do open heart surgeries in young age for their children. Our study doesn't provide definitive data about the prevalence of congenital heart disease (CHD) in adults; it gives an indirect picture of CHD in adult patients and its correlation with age.

In one of studies which were carried out on 2004 concerned in the follow up of cases, they found the predominated GUCH cases were VSD 31% and ASD 29%. Pulmonary and aortic stenosis, aortic coarctation, and complex congenital heart disease were less frequent. 75% of these cases presented with small lesions, which permitted the normal development of the patient and did not require specific therapy, 17% patients presented lesions of considerable impact and were waiting for cardiovascular intervention at the time of the study [12].

Because of that, we were concerned with the ASD cases as one of the predominant congenital cardiac lesion reaching adulthood. In our study some of the patients were asymptomatic and can survive easily to adulthood, unless, there is an associated lesion, or the balance between pulmonary and systemic circulation start to disturb. This was supported by many literature reviews, as ASD is the commonest congenital heart anomaly that can be seen in the adult age and secundum type is the most presented type of ASD. A physical examination of a patient with ASD usually reveals subtle findings, and hence the diagnosis may be missed [16].

The diagnosis was established by TTE in the majority of cases and only TEE was requested to confirm the diagnosis as they were of high BMI more than 35. Other studies confirmed the use of echocardiography for diagnosis as slandered technique. Cardiac catheterization is wasn't necessary to complete the diagnosis but remains a critical technique for evaluation of irreversible pulmonary hypertension or for detecting underlying coronary artery atherosclerosis and for planning interventions, this is supported by other studies for adult CHD [17,18].

The use of coronary angiography was performed on all patients over 40 years of age and high risk cases for ischemic heart disease. Right heart catheterization were done for cases with sever pulmonary hypertension more than 50 mmHg to exclude cases with irreversible pulmonary vascular resistant. Other investigators found 4% of cases had Eisenmenger syndrome secondary to the congenital heart defect, which rendered surgery impossible, whereas 4% had a significant lesion and rejected the surgery [12].

In this study there were variable presentations at the time of examination pre-operative, the most significant manifestations were palpitation and dyspnea and their impact on exercise intolerance and easy fatigability. The occurrence of stroke secondary to paradoxical emboli was documented in our cases encouraged surgery to avoid repeated cerebrovascular accidents. The findings were similar to other studies concerned in these symptoms and concluded that, the indications for closure in the pediatric and the adult population is essentially the same. In pediatric patients, however, primary attention is directed to symptomatology of recurrent respiratory tract infections and failure to thrive. In adults, respiratory symptoms such as shortness of breath tend to occur [19,20].

Classic sternotomy still the traditional approach to the heart, it was used in the majority of cases in both groups of cases, as most of the surgeons are not familiar with minimal invasive approaches either due to insufficient training or lake of facilities. Thoracotomy was used to less extent in cases of both groups in this study. Thoracotomy cases showed better recovery, more cosmetic satisfaction and decreasing the risk of sternal wound infection and sternotomy pain. The use of Fibrillator was used in a good number of cases in both groups comparable to the use of routine cardioplegic solution. In other study, all patients either post sternotomy or thoracotomy recovered rapidly from the surgery. Follow-up was complete in all patients, with no late complications and no residual shunt post ASD repair [21].

Regarding palpitation secondary to AF or SVT, was sharply decline post-surgical repair, confirmed with ECG. This coincides with the results of some authors who mentioned that surgical repair of ASD is a useful treatment in adult patients, because it improves hemodynamic status and normalize PAP, independent of age at the time of repair [22].

Pulmonary arterial hypertension, defined as a mean pulmonary arterial pressure greater than 25 mmHg at rest or greater than 30 mmHg during exercise [23]. According to this definition, most of our patients have pulmonary hypertension at presentation, Pulmonary artery pressure showed significant reduction post-operatively in both groups of cases with valuable reduction in group I, denoting correlation between age and PAP improvement post ASD closure. Some studies demonstrated in their work, 10% to 41.8% of patients developed pulmonary hypertension in varying degrees in adults with congenital heart diseases [8,23,24]. Also, an interesting reference in the work of some authors, who supported that in a number of adults even with severe hypertension pre-operatively, had a good post-operative course [25].

The principal consequence of ASD is a volumetric overload of the small annuli that causes progressive dilatation of the right ventricle and increases pulmonary pressure. These hemodynamic effects may be well tolerated for decades, but eventually cause right ventricular dysfunction and cardiac insufficiency. Tricuspid valve insufficiency secondary to annular dilatation is produced, that aggravate the sequences of ASD in adults [26]. Based on that Echocardiography was beneficial in follow up of cases pre and post-operative and confirmed the significant regression in the degree of tricuspid valve regurgitation. When the ASD is closed before the age of 18 years, the majority of these changes normalize [12,27]. This coincides with our results that encourage surgery without delay.

In our study the morbidities as bleeding, pericardial effusion and wound infection were documented in both groups and there percentage were more in group II than group I, This correlations between the morbidities and age of patients were documented in other literatures concerned in post-operative complications [28].

Mortality was low among our cases as it was 0.61%, deaths occurred in 2 cases in group II and one case in the group I. Some authors estimated the mortality in their study, it was 3.3% all of them were in the older age group as well [14]. The mortality was much less with other research studies in young patients [29,30].

Throughout the 40 years over which surgical correction has been carried out, peri-operative mortality has decreased from 12.5% in the late 1950 s to 6% in the 1960 s, and to below 0.5% today [30]. This major improvement in survival appears to be a reflection of both better operative technique and better post-operative care, so surgical closure of this relatively common anomaly became widely recommended even for older patients.

Surgeries were done in these adult cases once diagnosed and according to pre-operative evaluation. This is confirmed with others who suggested that, surgery should be performed in the younger patient and probably before structural changes in the myocardium or pulmonary vasculature may start [31]. Surgery performed in our cases in both groups of cases after exclusion of irreversible pulmonary hypertension and this is supported by others who found that, age was a significant and independent predictor of surgical mortality and morbidity at late follow up [13].

Regarding the use of sildenafil, it showed significant improvement in PAP post-operative in both groups who received the medication. Literatures concerned about sildenafil found that, mid-term oral sildenafil therapy led to significant improvement in pulmonary hemodynamics, functional class and/or exercise tolerance [32,33]. Its use still need work up to prove its efficacy in pulmonary hypertension secondary to congenital heart defects.

Surgery for ASD in the adult age is a safe, beneficial, and a low-risk option that modifies the patient’s natural history by improving their clinical status. The operation must be performed without major delay, better to be in established GUCH centers by well trained staff. Despite the use of sildenafil is still need more research. It seems to have good result post-operative.

Consent for publication

Written informed consent was obtained from the patients for publication of this study. The consents are available for review by the Editor-in-Chief of this journal.

Availability of data and materials

The data sets during the current study are available from the corresponding author on reasonable request.

Authors contributions

AS, MA and HE: Collected clinical materials of these patients, participated in the design of the study and performed the statistical analysis. EE: participated in the study design, data analysis and study coordination. All authors contributed to preparation of the clinical data used in this paper and revised the manuscript critically. All authors read and approved the final manuscript.