Keywords

Introduction

Atrial septal defects (ASDs) facilitate continuous left to right intracardiac shunting. The magnitude of this shunt and the hemodynamic effects of the left to right shunt determine the indications for closure of the ASD. The guidelines for ASD closure are largely accepted in the current era [1]. However, many practicing physicians may be less familiar with the effects of untreated ASDs and the evidence for their management as much of this research was conducted some decades ago.

The patent foramen ovale (PFO) represents the potential for small, intermittent, and potentially provocable right to left shunting. The PFO must therefore be considered as a potential source of venous to arterial transmission of particulate or chemical products and be managed based on the associated clinical syndrome rather than on its anatomical characteristics. As there is a continuum in the magnitude of shunting along the spectrum of defects of the interatrial septum, the physician confronted with an interatrial shunt first considers the potential of flow mediated disease. If the shunted blood flow is felt not to represent an indication for closure as is the case with most PFOs, the defect should be considered in terms of its potential for PFO mediated syndromes, including migraine, stroke, deep sea diving and decompression related disorders, platypnea orthodeoxia and exercise desaturation, obstructive sleep apnea, and a number of clinical concerns in the perioperative period.

Atrial Septal Defects

The long-term physiologic effects of large untreated ASDs are fortunately rarely observed in the developed world today. As an early indication for cardiac surgery, the observational ASD literature dates to the 1960s. Craig and Selzer reported a series of 128 consecutive adults with large ASDs in 1968 [2]. While 50 patients demonstrated pulmonary to systemic shunt ratios (QP:QS) over 3:1, the defect size and magnitude of shunting was only marginally predictive of the development of pulmonary hypertension. Among the 13 % of patients who developed pulmonary hypertension before the age of 40, many had underlying contributors such as mitral stenosis. The majority of patients developed atrial arrhythmias and dyspnea in their 50s and 60s with diminished survival. The nonrandomized observational literature similarly points to improved survival among patients with large ASDs who undergo surgical repair compared to matched controls managed medically [3]. More recently, marked reduction or normalization of right heart enlargement and pulmonary hypertension is usually observed after transcatheter closure of ASDs [4].

The guidelines endorsed by the American College of Cardiology (ACC) and American Heart Association (AHA) support closure of ASDs when there is enlargement of the right atrium or right ventricle with a class IB level of support [1]. Neither the anatomic size, shunt ratio, nor pulmonary hypertension are noted in these guidelines. The guidelines note that “small ASDs with a diameter of less than 5 mm and no evidence of RV volume overload do not impact the natural history of the individual and thus may not require closure unless associated with paradoxical embolism… Symptoms may develop with increasing age even with small defects (less than 10 mm) owing to an increase in shunting caused by a decrease in LV compliance secondary to coronary artery disease, acquired valvular disease, or hypertension.”

Migraine

There is a well described association between PFO and migraine, particularly migraine with aura; whether this is a causal relationship remains controversial [5]. Putative mechanisms for the genesis of aura and headache in migraine include paradoxical microembolism or increased concentrations of serum chemicals due to the bypass of pulmonary filtering of venous blood. Furthermore, there is clinical trial data to support PFO closure in patients with migraine, although convincing prospective randomized and controlled clinical trial data is absent.

Stroke

PFO is more common in patients with cryptogenic stroke than in the general population, suggests a causal relationship [6]. This is supported by multiple case reports of thrombus visualized within the tunnel separating the septum primum and secundum in the setting of embolic stroke [7]. Therefore, surgical and percutaneous PFO closure has been explored as a treatment option to prevent paradoxical embolism in patients with prior cryptogenic stroke. Limited clinical trial data suggests that closure may be more effective than antiplatelet therapy or systemic anticoagulation in selected subgroups [8].

Deep Sea Diving

Decompression illness may occur in divers who ascend too quickly after diving to a significant depth, resulting in bubble formation due to precipitation of gas in the venous circulation. PFO may be an important and reversible risk factor for decompression illness complicated by arterial gas embolism and closure may be considered to prevent recurrence [9].

Orthodeoxia/Platypnea

Orthodeoxia/platypnea is an uncommon clinical syndrome of dyspnea and deoxygenation when transitioning from a lying to a sitting or standing position. It is thought that two conditions must exist for this rare clinical entity to exist: a right-to-left shunt at the level of the interatrial septum and a structural or functional factor that results in increased shunt when standing.

Similarly, desaturation may occur during exercise when exertion increases venous return sufficiently to provoke enough right to left shunting to induce hypoxia. The phenomena of provoked exercise desaturation is relatively common among young patients with PFO associated stroke or migraine and may improve following PFO closure [10].

Sleep Apnea

PFO may be a risk factor for obstructive sleep apnea, although the reasons for this possible causal association remain poorly defined and controversial [11]. More importantly, PFO may exacerbate nocturnal hypoxemia and pulmonary hypertension in patients with obstructive sleep apnea [PMID: 22924163]. Also, considering that the risk of stroke is increased in patients with obstructive sleep apnea, paradoxical embolism through a PFO may be the etiology of these strokes. This is another reason why PFO closure has been proposed in this patient population.

Approach to the Patient with an Intracardiac Shunt

The list of potential indications for PFO closure requires a consistent and structured approach to both the anatomy of the interatrial septum and functional significance of the PFO anatomical variants. Shunting across the interatrial septum may be fixed or vary with the relative right and left atrial pressures which are in turn influenced by volume, posture, and changes in intrathoracic pressure. Shunting of blood across a defect of the interatrial septum may be right-to-left, left-to-right, or bidirectional. Quantification of the severity of shunt is important. Finally, assessment of the consequences of the shunt is critical.

Therefore, a young woman with no pulmonary pathology who presents with shortness of breath, an atrial septal defect, fixed bidirectional shunting and right ventricular enlargement would be considered for percutaneous or surgical closure. However, an elderly man with history of myocardial infarction who presents with a focal neurological deficit and has a PFO with intermittent right-to-left shunting (rest versus Valsalva) of minor severity (echocardiogram or TCD) and no imaging evidence of embolic cerebrovascular event poses a much more difficult management dilemma. The more in-depth discussion of these clinical syndromes that follows will attempt to characterize our understanding of these conditions and guide sensible management decisions.