Refractory hypoxemia following mitral valve edge-to-edge repair: why is it so refractory?

Abstract

Transcatheter Edge-to-Edge Repair (TEER) is an established therapy for high-surgical-risk patients with severe mitral regurgitation (MR). Iatrogenic atrial septal defects (iASD) are a routine consequence of transseptal puncture, and significant right-to-left shunting (RLS) causing refractory hypoxemia is rare. This report presents a man in his 80s with multiple comorbidities who underwent successful surgery. Despite procedural success confirmed by transesophageal echocardiography (TEE), the patient developed refractory hypoxemia during the early recovery phase while still undergoing mechanical ventilation. Normal airway pressures and partial pressure of end tidal carbon dioxide (PETCO₂) ruled out common pulmonary causes. Postoperative transthoracic echocardiography (TTE) revealed a right-to-left shunt via an iASD, which was promptly closed percutaneously, resulting in rapid resolution of hypoxemia. This report highlights that severe hypoxemia following successful TEER should trigger a suspicion of a RLS, especially in patients receiving mechanical ventilation with positive end-expiratory pressure (PEEP) or anemia. Early recognition and consideration of defect closure is essential when hypoxemia is refractory to conventional ventilatory maneuvers.

Introduction

Transcatheter Mitral Valve Edge-to-Edge Repair (TEER) has become a cornerstone therapy for patients with severe mitral regurgitation (MR) deemed at high surgical risk [1]. The fundamental step in TEER is the transseptal puncture, which inevitably creates an iatrogenic atrial septal defect (iASD). Typically, this type of defect is benign. However, a rare but potentially fatal complication can arise when this hemodynamic balance is disrupted. In patients with pre-existing right ventricular dysfunction or pulmonary hypertension, the acute unloading of the left ventricle following TEER can paradoxically reverse the interatrial pressure gradient. This “hemodynamic flip” facilitates a right-to-left shunt (RLS), leading to refractory hypoxemia. However, the triggers that transform the defect into a life-threatening crisis remain complex and multifactorial.

We report the case of a patient who developed profound, refractory hypoxemia immediately following a technically successful TEER procedure under general anesthesia. This case reminds anesthesiologists: when procedural success (elimination of MR) is met with respiratory collapse, one must look not only beyond the lungs and the intracardiac shunt unmasked by altered hemodynamics, but also specifically at ventilatory strategies and the physiological impact of anemia.

Case presentation

A man in his 80s with New York Heart Association (NYHA) class IV heart failure was admitted with a 3-year history of recurrent dyspnea and chest tightness that had worsened over the preceding month. His medical history was significant for atrial fibrillation, chronic kidney disease, hyperuricemia, hypocalcemia, hypoalbuminemia, and severe anemia (hemoglobin, 5.4 g/dL [54 g/L], hematocrit, 17.7% [0.177]). Preoperative transthoracic echocardiography (TTE) revealed severe mitral regurgitation (MR), severe tricuspid regurgitation, and global cardiac enlargement. As is common in patients undergoing TEER, this patient also had pulmonary hypertension, with a mean pulmonary artery pressure (mPAP) of 22.3 mmHg, and associated right ventricular dysfunction.

Therefore, the patient underwent TEER under general anesthesia with endotracheal intubation. Anesthesia induction was performed using ciprofol, sufentanil, and rocuronium, and maintained with sevoflurane, ciprofol, and remifentanil. Vasoactive support was maintained with continuous infusions of norepinephrine and dobutamine, supplemented by intermittent boluses of phenylephrine as required to ensure hemodynamic stability. Intraoperative monitoring included invasive blood pressure monitoring and continuous transesophageal echocardiography (TEE) for procedural guidance. A lung protective ventilation strategy with a tidal volume of 5–6 mL/kg, a Positive End-Expiratory Pressure (PEEP) of 5 cmH₂O was employed. The total procedural duration was approximately 90 min, during which 400 mL of crystalloid solution was administered, with an estimated blood loss of 20 mL. Immediate echocardiographic evaluation confirmed that the mitral regurgitation was successfully reduced to mild severity, with a vena contracta width of 1.2 mm and a mean transmitral gradient (MG) of 2 mmHg measured by continuous-wave Doppler. The procedure was technically successful.

During the immediate recovery phase, following the routine removal of the TEE probe after successful device deployment but still being intubated and receiving mechanical ventilation, his oxygen saturation (SpO₂) began to decline progressively. Despite increasing the fraction of inspired oxygen (FiO₂) to 1.0 and performing manual recruitment maneuvers, the SpO₂ remained refractory, trending downwards to the lowest SpO₂ of 55% (Fig. 1A). Crucially, his airway pressures remained unchanged, and partial pressure of end tidal carbon dioxide (PETCO₂) was stable within the normal range. This clinical picture—severe hypoxemia with normal ventilation mechanics and stable PETCO₂—strongly argued against common postoperative complications such as pneumothorax, severe atelectasis, or massive pulmonary embolism.

Fig. 1.

(A) Changes of SpO2 during the whole procedure. (B) TTE image after TEER. TTE revealed a significant RLS with a diameter of 5.86 mm. (C) X-ray image after the whole procedure.

Suspecting an intracardiac etiology, and as the TEE probe had been withdrawn, a postoperative transthoracic echocardiogram (TTE) was immediately performed, which revealed a significant RLS across the iASD (diameter: 5.86 mm), driven by the altered interatrial pressure gradient (Fig. 1B). Following an emergency multidisciplinary discussion, percutaneous closure of the iASD was indicated. The response was instantaneous: the SpO₂ increased rapidly to 100%, and hemodynamic stability was maintained.

The patient was transferred to the Coronary care unit (CCU) and underwent follow-up radiography (Fig. 1C) and echocardiography. Follow-up echocardiography confirmed a marked reduction in mitral regurgitation (EROA 0.2 cm², regurgitant volume 29 mL), with no evidence of residual atrial-level shunting. However, aortic, tricuspid, and pulmonary regurgitation persisted, along with pulmonary hypertension (mPAP = 25 mmHg). Upon admission to the ICU, his hemoglobin was 7.8 g/dL [78 g/L]. Accordingly, 2 units of packed red blood cells were transfused perioperatively to correct his anemia. The patient was successfully extubated two hours postoperatively in CCU. Meanwhile, the patient initially required non-invasive ventilation for respiratory support, which was then transitioned to high-flow nasal cannula oxygen therapy with an inspired oxygen concentration (FiO2) of 50% and a flow rate of 50 L/min. The patient subsequently stabilized, was transferred to the general ward on day 8, and was fully discharged on day 28.

Discussion and conclusions

Postoperative hypoxemia under general anesthesia arises from multifactorial mechanisms [2, 3], with atelectasis remaining the primary cause. While the creation of an iASD is standard for TEER, the mechanism of hypoxemia is often associated with a “hemodynamic paradox” stemming from that defect. Effective clipping of the mitral valve led to an abrupt unloading of the left atrium, causing a precipitous drop in the left atrial pressure. Conversely, the patient’s pre-existing pulmonary hypertension and right ventricular dysfunction prevented a synchronous decline in right atrial pressure, where ventricular failure combined with severe tricuspid regurgitation further sustained or compounded the elevation of right atrial pressure. This discordance instantly reversed the interatrial pressure gradient, forcing deoxygenated blood from the right to the left atrium. However, previous studies [4] have reported that approximately 5% of patients undergoing TEER with the MitraClip system develop RLS through an iASD, with nearly one-third manifesting acute hypoxemia. And a multicenter study found that only 1% required percutaneous iASD closure due to severe hypoxemia or right heart failure and 73% of these interventions were necessitated within 24 h [5]. This indicates that while post-TEER iASD is common, the development of refractory, life-threatening hypoxemia remains rare, appearing only when the hemodynamic balance is severely tipped.

A prior case report [6] described a patient with an iASD following TEER whose PaO₂/FiO₂ ratio declined markedly. Notably, his peripheral oxygen saturation (SaO₂) was successfully maintained within the normal range by escalating the FiO₂. However, this approach failed in our patient. The severity of the hypoxemia in our case was likely exacerbated by a “double hit” phenomenon involving severe anemia and a mechanical ventilation strategy. Besides, the delay of the hypoxemia is primarily attributed to a combination of mechanical and hemodynamic factors. Intraoperatively, the iASD was physically occluded and masked by the TEER delivery system, rendering the interatrial shunt unremarkable during initial TEE monitoring. Following the withdrawal of the delivery system, the application of PEEP and progressive hemodynamic evolution of left atrial unloading, synergistically amplified the right-to-left shunt, leading to the profound post-procedural desaturation.

The patient’s significantly reduced hemoglobin level compromised the arterial oxygen content. According to the shunt equation, in the presence of a fixed shunt fraction, a lower mixed venous oxygen saturation (SvO₂)—secondary to anemia—results in a disproportionately severe desaturation of arterial blood. The severe baseline anemia, coupled with surgical blood loss and crystalloid fluid shifts, substantially compromised the patient’s systemic oxygen delivery. This physiological vulnerability drastically narrowed his reserve to tolerate the anatomical right-to-left shunt, leading to the severe desaturation observed. Concurrently, anesthesia-induced atelectasis contributes to a ventilation-perfusion (V/Q) mismatch, reducing the patient’s physiological reserve to tolerate the shunt. Most anesthesiologists consider the PEEP as the standard intervention for atelectasis-induced hypoxemia, which can be detrimental in the presence of an iASD. In the present case, the patient was still under mechanical ventilation during the recovery phase. Excessive intrathoracic pressure may increase pulmonary vascular resistance, thereby increasing the right ventricular afterload and right atrial pressure. This can paradoxically worsen the RLS. Therefore, anesthesiologists must be cautious; when hypoxemia is refractory to modest PEEP in post-TEER patients, one should pivot to evaluating cardiac shunts rather than escalating ventilatory pressures blindly. This complex interplay explains why the hypoxemia was refractory to recruitment maneuvers and 100% oxygen, as these interventions address V/Q mismatch but cannot correct an anatomical shunt.

As TEER procedures become more common, anesthesiologists will frequently encounter iASD. This case highlights that standard ventilatory maneuvers, such as PEEP, can paradoxically exacerbate RLS in patients with borderline hemodynamics and anemia. Early recognition and prompt closure of defects are important.

Abbreviations

TEER

Transcatheter Edge-to-Edge Repair

MR

Mitral regurgitation

iASD

Iatrogenic atrial septal defects

RLS

Right-to-left shunting significant

TEE

Transesophageal echocardiography

PETCO₂

Partial pressure of end tidal carbon dioxide

NYHA

New York Heart Association

mPAP

Mean pulmonary artery pressure

PEEP

Positive End-Expiratory Pressure

CCU

Coronary care unit

V/Q

Ventilation-perfusion

Author contributions

Liming Yang collected the clinical data and drafted the manuscript. Jiantong Shen contributed to the anesthesia management and manuscript revision. Shihong Wen supervised the case and finalized the manuscript. All authors read and approved the final version.

Funding

Not applicable.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Ethical approval for this case report was provided by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. The patient provided written consent for the publication of this case report.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. This work followed the CARE guidelines from the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network.

Competing interests

The authors declare no competing interests.