In females with unoperated atrial septal defects, pregnancy is usually well tolerated and can be allowed to continue. The effect of the increased cardiac output on the volume-loaded right ventricle in patients with left-to-right shunts may be counterbalanced by the decrease in peripheral vascular resistance. There is a small risk of paradoxical emboli, stroke, arrhythmias and, if the defect is very large, heart failure [40]. In the absence of pulmonary hypertension, maternal complications are infrequent [41, 42]. However, Yap et al. reported that pre-pregnancy history of arrhythmias and maternal age older than 30 years were risk factors for maternal cardiac complications [42]. The outcome of the babies from the pregnancies was similar to the general population. In females with atrial septal defects and severe pulmonary hypertension, pregnancy should be avoided, because the maternal mortality may be high [42]. In the study by Bedard et al., maternal deaths occurred soon after delivery and were due to congestive heart failure, thromboembolism, pulmonary hypertensive crisis and sudden cardiac death [43]. It is therefore very important that young women of childbearing with atrial septal defects should undergo thorough evaluation before undertaking a pregnancy, so that their management can be optimised or the defect closed. Percutaneous closure of ASD during pregnancy should be considered only when they are thought to be responsible for neurological events due to paradoxical embolism in the presence of deep vein thrombosis not cured with anticoagulation or in the presence of heart failure.

Patent foramen ovale (PFO) is usually of no clinical significance as it is found in up to 25 % of the adult population [44]. However, it may be a contributing factor in cryptogenic strokes and migraine. In order to prevent cryptogenic strokes, various studies have been performed to close patent foramen ovale by catheter techniques using a variety of devices. Similarly, studies were performed to assess whether patent foramen closure improved migraine also.

In cryptogenic strokes, it is thought that manoeuvres, which increase the right atrial pressure above the left atrial pressure, causing a right-to-left shunt, such as coughing, exercise and performing Valsalva manoeuvre, may increase the propensity to a stroke in patients susceptible to peripheral vein or right atrial thrombosis. Although patent foramen ovale may not be associated with any increased morbidity in the normal population, it has been reported that patients who have had cryptogenic strokes may have an increased prevalence of patent foramen ovale than those in whom the cause of the stroke has been identified, such as atherosclerotic disease [45–48]. The presence of a large patent foramen ovale and atrial septal aneurysm may predispose to a higher occurrence of strokes [49, 50]. Although patients with strokes may be treated with antiplatelet agents or anticoagulants, there may be serious side effects associated with these, such as haemorrhage or inability to tolerate these drugs. This is even more important in young patients [54].

There are also many unresolved issues. In patients more than 55 years of age, careful assessment of the atherosclerotic risk factors is important. If more than three risk factors are present, it is very unlikely that the cause of stroke is venous thromboembolism, and PFO may not be a contributory factor. In these patients, atrial fibrillation needs to be excluded. Implanting a loop recorder for one year to identify episodes of paroxysmal atrial fibrillation before PFO closure may be helpful. A clear indication for PFO closure is stroke during Valsalva manoeuvre in the presence of deep venous thrombosis. Another indication is platypnoea-orthodeoxia syndrome, which is characterised by arterial desaturation worsened by the upright position. It may be due to an atrial deformation caused by factors such as pneumonectomy or ascending aortic aneurysm. In the upright position, stretching of the interatrial septum leads to a permanent opening of the PFO with a large right-to-left shunt. This syndrome may be cured by PFO closure.

It is also debatable whether the closure of PFO as primary prevention of air embolism in divers is useful. It may be useful in professional deepwater (under 40 m) divers.

Migraine may occur in up to 17 % females and 6 % of males and may cause important morbidity to patients [51, 52]. The mechanism of how patent foramen ovale may contribute to migraine is poorly understood. One small randomised study, Migraine Intervention With STARFlex Technology (MIST) trial, with closure of PFO with StartFlex technology, failed to demonstrate complete cessation of migraine six months after PFO closure, compared with medical treatment. Anzola et al. reported the incidence of patent foramen ovale with right-to-left shunting in 48 % of patients who experienced migraine with aura, compared with 23 % in those without aura and 20 % of normal control subjects, possibly identifying a subset of patients, in whom closure of the patent foramen ovale may be beneficial [53]. However, no clear consensus has been reached on the treatment of migraine with closure of PFOs.

Device closure of PFO is a low-risk procedure; however, there are some rare but important complications, such as device embolisation, erosion, residual shunting through the device or the foramen, arrhythmias and, most importantly, thrombus formation [55]. A variety of devices have been used to close the PFO, and data have been collected and reported, but still some technical issues remain. Lipomatous septum secundum can be a problem, because the device, which embraces this large septum, often leaves residual shunts. Also very long and narrow tunnels can nowadays be dealt with by a separate transeptal puncture to close the defect properly, avoiding distortion of the septum.

Three randomised trials have been performed in patients with cryptogenic stroke to assess the superiority of device closure over medical treatment. In CLOSURE 1, 909 patients were randomised to device closure or medical treatment [56]. In this trial, there was no significant difference between the two groups with regard to the primary end points of death, recurrence of stroke or transient ischaemic attacks. The RESPECT trial comparing medical treatment with device closure using the Amplatzer PFO device (St. Jude Medical, Minneapolis, MN) showed a relative risk reduction of stroke in the patients treated with a device compared with medical treatment, but this was not significant [57]. The 10-year follow-up (mean 5.5 years) results of this trial (presented at TCT 2015) showed that in the intention-to-treat population, the relative risk for recurrent cryptogenic stroke was reduced by 54 % after PFO closure. Furthermore, an additional sensitivity analysis of all-cause stroke in young patients (less than 60 years of age), in whom the strokes are most likely to be cryptogenic, showed a 52 % relative risk reduction. Additional benefit was also seen in a subgroup of patients with a substantial shunt or atrial septal aneurysm, in whom there was a 75 % reduction in cryptogenic stroke risk.

Currently in the patients, who continue to have recurrent strokes despite medical treatment, device closure is an acceptable option. Controversy remains about how to manage patients, who have had a single stroke and have a patent foramen ovale. Further studies on selected population (young patients with no risk factors) and longer follow-up are required.