Iatrogenic Atrial Septal Defect Requiring Transcatheter Closure Following Transcatheter Mitral Valve Repair

Yoichi Takaya; Teiji Akagi; Hidehiko Hara; Hideaki Kanazawa; Yuji Ikari; Akihiro Isotani; Shinichi Shirai; Shunsuke Kubo; Takao Morikawa; Toru Naganuma; Mike Saji; Shingo Kuwata; Go Hiasa; Yusuke Watanabe; Masahiro Yamawaki; Masao Imai; Takashi Matsumoto; Masanori Yamamoto; Tsutomu Murakami; Masahiko Asami; Isamu Mizote; Tsukasa Okai; Hiroki Bota; Hiroshi Ito

doi:10.1253/circj.CJ-22-0048

Abstract

Background: Transcatheter mitral valve repair with the MitraClip system has been established in selected high-risk patients. The MitraClip procedure results in a relatively large iatrogenic atrial septal defect (iASD). This study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.

Methods and Results: This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. The data of patients on whom transcatheter iASD closure was performed were collected. Of the 2,722 patients who underwent the MitraClip procedure, 30 (1%) required transcatheter iASD closure. The maximum iASD size was 9±4 mm (range, 3–18 mm). The common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Of the 30 patients, 22 (73%) required transcatheter closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure complicated with cardiogenic shock. Of the 5 patients, 2 required mechanical circulatory support devices. Twenty-one patients immediately underwent transcatheter iASD closure, and hemodynamic deteriorations were resolved; however, 1 patient died without having undergone transcatheter closure.

Conclusions: Transcatheter iASD closure was required in 1% of patients who underwent the MitraClip procedure. Many of these patients immediately underwent transcatheter iASD closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt.

Transcatheter mitral valve repair for severe mitral regurgitation has been developed as a therapeutic alternative to surgery in selected high-risk patients.¹ Transcatheter mitral valve repair with the MitraClip system (Abbott Vascular-Structural Heart, Menlo Park, CA, USA) leads to an improvement in clinical outcomes with respect to heart failure symptoms.² For the MitraClip procedure, transseptal puncture with a large sheath carries a risk of the development of a persistent iatrogenic atrial septal defect (iASD). Because iASD can induce hemodynamical consequences, its clinical relevance is being increasingly recognized. The incidence of iASD requiring transcatheter closure after the MitraClip procedure has been reported in case reports or single-center studies;³^–⁵ however, data from large cohort studies, including the indications for transcatheter closure, are limited. Therefore, this study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.

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Methods

Study Population

This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. We investigated the patients who underwent transcatheter closure of iASD following the MitraClip procedure in the institutions from April 2018 to November 2020, and collected the data of these patients. The MitraClip procedure was performed in patients with severe degenerative or functional mitral regurgitation, which was complicated by heart failure symptoms despite optimal medical therapy, who were at high-risk for surgery. The decision to perform transcatheter iASD closure was made by the physicians at each institution. Transcatheter iASD closure was performed on off-label use, which was approved by the ethical committee of each institution. This study was performed in accordance with the Declaration of Helsinki and approved by the ethical committee of our institution. Informed consent was obtained from patients before they entered this study.

Data Collection

We retrospectively collected the data of patients on whom a transcatheter iASD closure was performed; this included heart failure symptoms, transthoracic echocardiographic measurements, MitraClip procedure details, and transesophageal echocardiographic measurements. Transcatheter iASD closure details, including the timing of transcatheter closure, the clinical course, such as a large defect, right-sided heart failure with left-to-right shunt, pulmonary hypertension, or hypoxemia with right-to-left shunt, and device selection, were investigated. A large defect was defined as being >10 mm in diameter.⁶

Results

Patient Characteristics

Of the 2,722 patients who underwent the MitraClip procedure at the 59 institutions, 30 (1%) required transcatheter closure of iASD at 19 institutions. The clinical characteristics of the 30 patients are shown in Table 1. The mean age of patients was 77±11 years (range, 36–92 years). At baseline prior to the MitraClip procedure, 22 (73%) patients were in NYHA functional class III or IV. The mean left ventricular (LV) ejection fraction was 45±15%, and 10 (34%) patients had reduced LV ejection fraction of <35%. Eight (27%) patients had degenerative mitral regurgitation, and 22 (73%) patients had functional mitral regurgitation. Sixteen (53%) patients had severe tricuspid regurgitation. Twenty-nine (97%) patients underwent single transseptal puncture. Fourteen (47%) patients received an implantation of ≥2 clips.

Table 1. Clinical Characteristics of Study Patients

Age, years	77±11
Male	19 (63)
Body mass index, kg/m²	20.3±2.9
NYHA functional class III or IV	22 (73)
B-type natriuretic peptide, pg/mL	564±356
LV end-diastolic diameter, mm	57±9
LV end-systolic diameter, mm	44±10
Left atrial diameter, mm	56±12
LV ejection fraction, %	45±15
Tricuspid regurgitation grade
Mild	6 (20)
Moderate	8 (27)
Severe	16 (53)
Estimated RV pressure, mmHg	40±13
MitraClip procedure
Degenerative mitral regurgitation	8 (27)
Functional mitral regurgitation	22 (73)
Procedure time, min	143±76
Fluoroscopy time, min	40±27
Number of transseptal punctures
1	29 (97)
2	1 (3)
Number of clips
1	16 (53)
≥2	14 (47)

Data are presented as mean±standard deviation or n (%) of patients. LV, left ventricular; NYHA, New York Heart Association; RV, right ventricular.

Transcatheter iASD Closure

The maximum size of iASD following the MitraClip procedure ranged from 3 to 18 mm (Figure 1A). The mean maximum iASD size was 9±4 mm. The clinical course of transcatheter iASD closure is shown in Table 2. Some patients had multiple factors. The common clinical course was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. The iASD size was 10±4 mm in patients with left-to-right shunt and 8±3 mm in patients with right-to-left shunt. There was no relationship between the iASD size and left-to-right shunt or right-to-left shunt. Regarding the time of onset of iASD requiring transcatheter closure, 12 cases were in the 1st to 25th cases of the MitraClip procedure, 9 cases were in the 26th to 50th cases, and 9 cases were in the ≥50th cases.

Figure 1.

(A) Maximum iASD size following the MitraClip procedure. (B) Device size of the Amplatzer Septal Occluder used for transcatheter iASD closure. iASD, iatrogenic atrial septal defect.

Table 2. Clinical Course of Transcatheter iASD Closure

Large defect	10
Hypoxemia with right-to-left shunt	17
Right-sided heart failure with left-to-right shunt	13
Pulmonary hypertension	5

Data are presented as number of patients. iASD, iatrogenic atrial septal defect.

Of the 30 patients, 22 (73%) immediately required transcatheter iASD closure within 24 h following the MitraClip procedure. The other eight (27%) patients underwent transcatheter iASD closure after 24 h (Figure 2). Among the 22 patients requiring immediate transcatheter closure, 12 had hypoxemia with right-to-left shunt and 5 had right-sided heart failure with left-to-right shunt that was complicated by cardiogenic shock. Of the 5 patients having right-sided heart failure with cardiogenic shock, 2 were treated with mechanical circulatory support devices, such as veno-arterial extracorporeal membrane oxygenation or an intra-aortic balloon pump. Twenty-one patients immediately underwent transcatheter iASD closure, and the hemodynamic and clinical deteriorations were resolved after transcatheter iASD closure. However, 1 patient died of right-sided heart failure without transcatheter closure. The patient was an 86-year-old man with severe functional mitral regurgitation and LV dysfunction. After the MitraClip procedure, he developed right-sided heart failure due to right ventricular volume overload with left-to-right shunt, leading to low cardiac output syndrome. Transcatheter iASD closure could not be performed at the institution. He was treated for heart failure, including with an intra-aortic balloon pump, but died 6 weeks after the MitraClip procedure was performed. Among the 8 patients who underwent transcatheter closure after 24 h, 5 had hypoxemia with right-to-left shunt and 2 had right-sided heart failure with left-to-right shunt complicated by cardiogenic shock. Of the 2 patients having right-sided heart failure with cardiogenic shock, 1 was treated with veno-arterial extracorporeal membrane oxygenation and an intra-aortic balloon pump for low cardiac output syndrome, and 1 was treated with an intra-aortic balloon pump and Impella. After transcatheter iASD closure, the hemodynamic and clinical deteriorations were resolved.

Figure 2.

Timing and clinical course of transcatheter iASD closure. Twenty-two patients required transcatheter iASD closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure. Eight patients underwent transcatheter iASD closure after 24 h, including 5 with hypoxemia and 2 with right-sided heart failure. iASD, iatrogenic atrial septal defect.

Of the 29 patients who underwent transcatheter iASD closure, the device size was determined using transesophageal echocardiography in 27 patients and balloon sizing in 2 patients. An Amplatzer Septal Occluder (Abbott, Chicago, IL, USA) was used in 19 patients. The device size ranged from 6 to 17 mm (Figure 1B). An 18-mm Amplatzer Cribriform (Abbott, Chicago, IL, USA) was used in 2 patients, a 25-mm Amplatzer Cribriform was used in 3 patients, and a 35-mm Amplatzer Cribriform was used in 1 patient. A 7.5-mm Occlutech Figulla Flex II Occluder (Occlutech GmbH, Jena, Germany) was used in 2 patients, and a 9-mm Occlutech Figulla Flex II Occluder was used in 1 patient. There were no complications related to transcatheter iASD closure.

Discussion

The major findings of the present study were as follows: (1) transcatheter iASD closure was required in 1% of patients who underwent transcatheter mitral valve repair with the MitraClip system; (2) the common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt; (3) many of these patients immediately underwent transcatheter iASD closure; and (4) the hemodynamic and clinical deteriorations were resolved after transcatheter iASD closure. To the best of our knowledge, this is the first study to show the prevalence of iASD requiring transcatheter closure following the MitraClip procedure in a large cohort.

Transcatheter interventions involving transseptal puncture, such as pulmonary vein isolation and left atrial appendage closure, are increasingly being used in cardiology. Previous studies have reported the incidence of iASDs following these procedures.⁷^–⁹ Persistent iASDs in many of these studies were created using relatively small sheaths. The hemodynamic and clinical consequences are minimal, and therefore iASD closure is not routinely performed. Recently, transcatheter mitral valve repair with the MitraClip system has been established as a therapeutic option for the treatment of severe mitral regurgitation.¹ The MitraClip procedure requires transeptal puncture using a large sheath, resulting in a relatively large iASD.¹⁰

In terms of the hemodynamic consequences of iASD following the MitraClip procedure, some studies have shown worse outcomes, whereas other studies have shown no clinical significance. Schueler et al reported that persistent iASD occurred in 50% of cases at 6 months after the MitraClip procedure, and was associated with worse outcomes and high mortality rates.¹¹ Toyama et al reported that persistent iASD was associated with a high rate of hospitalization for heart failure;¹² however, as stated by the authors, it is unclear if iASD was a mediator or a marker of illness. Conversely, Smith et al reported that iASD was not hemodynamically significant.¹⁰ Ikenaga et al reported that iASD had no clinical impact on outcomes.¹³ Hoffmann et al stated that iASD might have a beneficial effect on left atrial pressure relief, contributing to a reduction of LV preload.¹⁴ Thus, variable findings have been observed in terms of clinical outcomes. Therefore, it is unclear whether transcatheter closure of iASD following the MitraClip procedure is beneficial. No guidelines currently exist for the management of iASD.

If iASD induces hemodynamic instability, transcatheter closure should be addressed. In the clinical setting, some case reports have shown iASDs requiring immediate transcatheter closure due to acute hemodynamic abnormalities. One study reported that patients developed significant oxygen desaturation with right-to-left shunt immediately after the MitraClip procedure, which was resolved by iASD closure.¹⁵ Another study reported that patients developed acute right-sided heart failure with left-to-right shunt, which was resolved by iASD closure.¹⁶ However, data on transcatheter closure of iASD following the MitraClip procedure are limited to case reports or single-center studies.³^–⁶^,¹⁵^,¹⁶ The prevalence of iASD requiring transcatheter closure, especially in the acute phase following the MitraClip procedure, and its clinical course remain unclear.

The present study showed that transcatheter iASD closure was required in 1% of patients who received transcatheter mitral valve repair. Many of these patients required immediate transcatheter closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Importantly, 1 patient died of right-sided heart failure with left-to-right shunt complicated with low cardiac output syndrome. In this case, the MitraClip procedure was appropriately performed. As the exacerbating factor for heart failure, we considered that left-to-right shunt caused by iASD also caused acute hemodynamic abnormalities in the state of serious illness, resulting in right-sided heart failure with low cardiac output syndrome. If the transcatheter closure of iASD could be performed, the hemodynamic deterioration might be prevented; however, immediate transcatheter iASD closure was not possible due to the unmet of the institutional requirements.

Transcatheter mitral valve repair is mainly performed at the advanced stage of heart failure, which is accompanied by reduced LV function and an increased LV end-diastolic pressure.¹⁷^,¹⁸ Patients selected for this procedure often have advanced illness. Although rare, significant shunting induced by iASD following the MitraClip procedure can easily lead to hemodynamic and clinical deteriorations. Furthermore, iASD caused by the MitraClip procedure results in relatively large shunting. In such conditions, immediate transcatheter iASD closure is required to improve hemodynamics after the MitraClip procedure. The present study included a high-risk population, with 73% of patients having functional mitral regurgitation in addition to an advanced stage of heart failure. This study clarified the prevalence and clinical course of iASD requiring transcatheter closure in real world settings. Our findings will be important when deciding the most suitable therapeutic strategy for all institutions performing the MitraClip procedure.

Study Limitations

First, this was a retrospective, observational study. The number of patients was relatively low. Large studies are needed to confirm our findings; however, this is the largest study for investigating iASD following the MitraClip procedure. Second, this was a case series report. Because we investigated only patients on whom transcatheter iASD closure was performed, this study did not have the data of patients who did not require transcatheter iASD closure. The differences in clinical characteristics between patients who did or did not undergo transcatheter iASD closure were not assessed. We did not indicate predictors requiring transcatheter iASD closure before the MitraClip procedure. Third, transcatheter iASD closure was performed at the discretion of treating physicians. Fourth, there might have been more patients who had right-sided heart failure without a recognized need for transcatheter closure of iASD, especially with those with a left-to-right shunt. We did not investigate this patient cohort. Finally, invasive hemodynamic data were not available.

Conclusions

Transcatheter iASD closure was required in 1% of patients who received transcatheter mitral valve repair with the MitraClip system. The common clinical course was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Many of these patients immediately underwent transcatheter iASD closure following the MitraClip procedure.

Disclosures

Y.I. and H.I. are members of Circulation Journal’s Editorial Team.

Sources of Funding

This study did not receive any funding.

Data Availability

This study is based on data from our institutions. The data are available from the corresponding author upon reasonable request.

IRB Information

This study was approved by the Ethics Committee at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (2008-013).

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