Tricuspid Regurgitation–Patent Foramen Ovale Coupling

Corresponding Author

Tricuspid regurgitation (TR) has gained increasing clinical importance in the last 10 years.¹ However, despite its prevalence, TR remains markedly undertreated, with an estimated 160,000 to 240,000 new cases in the United States each year but fewer than 10,000 receiving interventions.² Historically, the tricuspid valve was considered to be a passive structure, on the systemic venous side of the heart, without clinically significant function. Recent insights into TR highlight its significant impact on morbidity and mortality when left unaddressed.³

In this issue of JACC: Case Reports, Zorman et al⁴ present a compelling case of an 82-year-old man who developed acute breathlessness and cyanosis—symptoms that worsened when upright and improved while lying flat, classic for platypnea-orthodeoxia syndrome (POS). The patient was found to have torrential TR leading to a right-to-left shunting via a patent foramen ovale (PFO), a condition that was successfully treated with transcatheter PFO closure and tricuspid transcatheter edge-to-edge repair (TEER). This case underscores the critical interaction between TR and PFO in the pathogenesis of POS, suggesting that TR-PFO coupling might be more common than previously recognized, or perhaps, frequently overlooked.

POS is a rare clinical entity characterized by dyspnea (platypnea) and arterial desaturation (orthodeoxia) when in an upright position, which typically improves when lying flat.⁵ POS results from the mixing of oxygenated and deoxygenated blood, commonly caused by a right-to-left shunt at the atrial level, often through a PFO. Intracardiac causes like atrial septal defects (ASDs) or atrial septal aneurysms may also contribute to POS, as can extracardiac abnormalities such as pulmonary arteriovenous malformations or parenchymal lung diseases. Concerning PFO, flow across the PFO was significantly higher in the upright than the supine position, consistent with the lower oxygen saturation seen in the upright position.⁶

TR and PFO are common cardiac anomalies, but their combined impact on clinical outcomes remains underexplored. On the one hand, in the absence of left heart disease, the clinical signs and symptoms of severe TR, such as edema, fatigue, and exercise intolerance, are often mistaken for normal signs and symptoms of aging, leading to delays in diagnosis and treatment. On the other hand, PFO is prevalent in 20% to 25% of the adult population, and while most individuals with PFO remain asymptomatic, it has been strongly associated with cryptogenic stroke, especially in younger patients.⁷ Studies suggest that up to 50% of patients who experience cryptogenic stroke may harbor a PFO.⁷ This relationship is particularly important because PFO allows paradoxical embolism, in which a venous thrombus can pass through the ASD into systemic circulation, potentially leading to ischemic events like stroke. Anatomical factors such as the size of the PFO, presence of an atrial septal aneurysm, and the degree of shunt (right-to-left flow) all influence stroke risk. However, unlike in the case of a stroke, the size of the shunt in PFO plays a more prominent role in POS. Larger shunts are more likely to cause significant hypoxia in POS, while even small shunts are more likely to cause significant hypoxia in POS, while even small shunts can lead to cryptogenic stroke due to the embolic nature of the disease.

This case highlights the need for a deeper understanding of the hemodynamic relationships between TR, PFO, and the pathophysiology of POS. As Zorman et al’s case illustrates, torrential TR may unmask or exacerbate PFO-related symptoms, suggesting that this interaction is underrecognized in clinical practice.

This phenomenon raises the question: how many patients with TR also harbor an undiagnosed PFO? Should routine screening for PFO be considered in patients with severe TR, especially those who develop unexplained hypoxia or positional dyspnea? The coexistence of these two anomalies may be more common than previously thought, especially in elderly patients with comorbidities.

The management of concurrent valvular pathologies, particularly mitral regurgitation and TR, is a common clinical challenge. Untreated TR, even after successful mitral valve repair, can lead to worsening right-sided heart failure. Therefore, the question arises whether to treat both valves simultaneously or in a staged manner. Recent data suggest that simultaneous TEER of the mitral and tricuspid valves may offer better outcomes, including higher 1-year survival rates, compared with isolated TEER for either valve.⁸

Furthermore, in patients with iatrogenic ASDs resulting from transcatheter procedures, decisions regarding ASD closure are complex. Immediate closure may not always be warranted, especially in patients with severe TR, as it can exacerbate right-sided pressures. In such cases, a conservative approach with close monitoring may be preferred, or ASD closure can be performed concomitantly with valvular repair if hemodynamics warrant it.

This highlights the need for individualized treatment strategies tailored to the patient’s specific hemodynamic and clinical context. Future studies should focus on identifying the optimal timing and sequencing of interventions in patients with multiple coexisting valvular and septal abnormalities.

Historically, POS has been managed through surgical correction of the intracardiac shunt, most commonly via PFO closure.⁵ However, in recent years, transcatheter techniques have gained prominence as safer and less invasive alternatives. Zorman et al treated their patient using a combined transcatheter approach—closure of the PFO with a GORE Cardioform Septal Occluder and TR correction with 2 PASCAL Ace devices (Edwards Lifesciences) for edge-to-edge repair. This tailored approach resolved the patient’s hypoxia, restored normal oxygen saturation, and addressed the underlying valvular dysfunction, all without the need for open-heart surgery.

This case highlights the utility of combined transcatheter interventions in addressing complex pathophysiological interactions between TR and PFO. TEER has emerged as a viable solution for TR, particularly in high-risk surgical patients, as it reduces the regurgitant volume, improves right heart function, and mitigates the risk of right heart failure. By simultaneously treating the PFO, the clinicians also eliminated the hypoxia-inducing shunt, offering a comprehensive solution to a complex problem.

Funding Support and Author Disclosures

Dr Chen has received grant support from Boston Scientific and Edwards Lifesciences; and served as a consultant for Jenscare Scientific. Dr Taramasso has served as a consultant for Abbott Vascular, Boston Scientific, Edwards Lifesciences, Medtronic, Pi-Cardia, CoreQuest, Shenqi Medical, Ventrimend, HiD Medical, Simulands, MEDIRA, and CoreMedic.