Percutaneous closure of ventricular septal rupture after myocardial infarction: A retrospective study of 81 cases

Abstract Objective To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI). Methods This retrospective study included 81 patients who underwent transcatheter closure for postinfarction VSR. We analyzed clinical data from hospitalization and the 30‐day follow‐up, compared clinical data from the survival and death groups, and explored the best closure time and the safety and efficacy of occlusion. The risk factors for death at 30 days were analyzed by logistic regression. Results C‐reactive protein (CRP), white blood cell counts, N‐terminal pro brain natriuretic peptide (NT‐ProBNP), and aspartate aminotransferase were higher in the death group than in the survival group (p < .01), with a higher rate of application of vasoactive drugs, and a shorter time from AMI to operation (p < .05). At 30 days postocclusion, 19 patients (23.5%) had died. The mortality rate was significantly lower for operation performed 3 weeks after AMI than for operation performed within 3 weeks of AMI (12.5% vs. 48%, p < .001). Devices were successfully implanted in 76 patients, with 16 (21.1%) operation‐related complications and 12 (15.8%) valve injuries. Cardiac function improved significantly (p < .001) at discharge (N = 66) and 30 days after procedure (N = 62). Qp/Qs and pulmonary artery systolic pressure decreased significantly, while aortic systolic pressure increased significantly (p < .001). Additionally, EF and LVDd improved (p < .05) after occlusion. Increases in CRP and NT‐ProBNP were risk factors for death at 30 days after closure (p < .05). Conclusion Percutaneous VSR closure can be a valuable treatment option for suitable patients with VSR.


| INTRODUCTION
Ventricular septal rupture (VSR) is a rare mechanical complication after acute myocardial infarction (AMI), occurring in approximately 0.26% of patients with acute coronary syndromes. 1 It has a high mortality rate in the early stages, approximately 67%−82% within 1 week of conservative treatment with drugs, and a 1-year survival rate of only 7%. 2,3 Surgical repair combined with coronary artery bypass grafting was previously used to manage patients with VSR, but there are limitations, such as a high perioperative mortality rate. 4 For patients with AMI complicated with VSR, surgical treatment might lead to a 30-day mortality rate of up to 47%. 5   The inclusion criteria were as follows. (1) AMI was diagnosed in accordance with the Universal Definition of Myocardial Infarction (fourth edited), 6 and the presence of VSR was observed on ultrasonography or ventriculography after AMI. (2) Informed consent was obtained from the patient/legal guardian.
The exclusion criteria were as follows. (1) Informed consent was not available from the patient or legal guardian, and the patient refused to comply with treatment or follow-up. (2) The defect had a diameter >22 mm or was very close to structures such as the valve or chordae tendineae, which was not suitable for closure. (3) The patient's cardiac function was not effectively controlled, and the patient was unable to maintain a supine position for more than half an hour. (4) The patient had other comorbid diseases with an expected lifetime of less than 1 year. (5) The patient had a history of infective endocarditis in the previous 3 months. (6) The patient had coagulation dysfunction that had not been effectively controlled.

The Ethics Committee of Fuwai Central China Cardiovascular
Hospital provided approval for the study.

| Interventional procedure
Basic procedures referred to the common view of Chinese medical experts on interventional treatment of ventricular septal defects. 7 Procedure steps: Deliver a 6 F pigtail catheter into the left ventricle near the apex, then perform left ventriculography at a left anterior oblique position of 35−50°and a cephalad position of 10°to assess the morphology, location, and diameter of the defect. Use a pigtail catheter at the cutting end or a JR 4.0 contrast catheter to assist in passing a super-slip guidewire through the defect to establish an arteriovenous track. Confirm the track is smooth under digital subtraction angiography to avoid loop tendon cords. Deliver the delivery sheath to the left heart system along the venous side of the track and release the occluder after it has been delivered along the delivery sheath to the appropriate position. Perform left ventriculography again to confirm that the occluder is fixed in position and well blocked, and then release the occluder. The closure device (A7B3H10) used here was from Shanghai Shape Memory Alloy Co. Ltd., as shown in Supporting Information: Figure 1, the closure device with a 7 mm left ventricular side rim (A), a 3 mm right ventricular side rim (B), and a 10 mm waist height (H). The diameter of the occluder was 8−14 mm larger than the perforation diameter, according to the size or the myocardial tissue weakness around the defect. Valve damage was defined as the occurrence of the above conditions.

| Statistical analysis
SPSS 22.0 was used to perform the statistical analysis. Measurement data that conformed to a normal distribution were represented by mean ± standard deviation and then analyzed with an independent sample t-tests for between-group comparisons or a paired sample t-test for within-group comparisons. For data with a skewed distribution, the data were expressed as the median (interquartile range) and analyzed with the U test. Comparisons of categorical variables in percent (%) were performed with the χ 2 test. Multivariate logistic regression analysis was conducted. A p value less than or equal to .05 was considered to indicate a statistically significant difference.

| General clinical information
There were 81 VSR cases with percutaneous closure, including 76 successful cases (93.8%) and 16 deaths at the 30-day follow-up.
There were 47 (58%) females with an average age of 67 (40−80) years. Patients who were discharged from the hospital were followed-up for 30 days and divided into a survival group and a death group according to the outcome. The general clinical data of the 81 patients are shown in Table 1.
In a comparison of the death and survival groups, CRP, WBC, NT-ProBNP, and AST were much higher in the death group (p < .01), and more patients in the death group received vasoactive drugs and mechanical circulatory support (MCS).
Compared to the survival group, the death group had a shorter time from AMI to VSR closure (p < .05), along with a lower success rate of the operation (p < .001). Among the VSR cases, culprit lesions were much more common in the anterior descending coronary artery, accounting for 80.2% of lesions, with the rest being in the right coronary arterial vessels. No patients with circumflex infarction were observed. All apical defects were caused by infarction of the anterior descending coronary artery, while most posterior septal defects were due to infarction of the right coronary artery. Only 2 posterior septal defects were caused by infarction of the anterior descending coronary artery (Table 1).

| Primary safety outcomes and timing of closure
Among the 81 patients who underwent percutaneous VSR closure, there were 19 deaths (23.5%) at the 30-day follow-up, including 15 in-hospital deaths and 4 out-of-hospital deaths. Five patients (6.2%) had failed occlusion, and all of these patients died in the hospital.
Among these 5 patients, 2 patients were scheduled for additional surgical repair due to loose tissue surrounding the defect and gradual expansion and dislodgement of the occluder after release, 2 patients could not closure for failed anchoring of the occluder as a result of a very large defect size (>20 mm), and 1 case was managed with another surgical repair because the delivery sheath during the operation was folded, and pericardial tamponade developed due to free wall rupture during correction. Detailed information on the patients with failed occlusion is presented in Supporting Information: Table. Primary endpoint outcomes were monitored after VSR closure performed at different time points. Since there were cases with unclear symptoms or delayed diagnosis of VSR on ultrasound, the diagnosis of VSR onset in this population is commonly not as accurate as the diagnosis of myocardial infarction. In this setting, we staged the time from AMI to VSR closure (T) as follows: T ≤ 2; 2 <T ≤ 3;   Table 2 for details.

| Effectiveness outcomes
All 76 patients with successful closure underwent ultrasound after the operation. There were 66 patients who completed the cardiac function assessment at discharge, and there were 10 in-hospital  Table 4 for details.

| DISCUSSION
VSR is one of the most severe mechanical complications after AMI.
Although thrombolysis or emergency PCI after AMI can contribute to a decreased incidence of VSR, there is still an exceedingly high mortality rate after VSR occurs. In the absence of active treatment, approximately 60%−70% of patients will die within 2 weeks after VSR, and no more than 10% will survive for 3 months. 8  reports, we found that the 30-day mortality rate of interventional VSR closure was better when performed 3 weeks after infarction compared to closure within 3 weeks of infarction (12.5% vs. 48%, p < .001). Additionally, we utilized the ROC curve method for the first time to calculate the optimal timing for VSR closure, which was found to be 21 days after MI. However, we only enrolled VSR patients who underwent operation, and those who died in the acute phase that were unable to receive interventional treatment were excluded, which may have resulted in selection bias.
The occluder should be selected according to the principal "large rather than small." Even if operated after 3 weeks, there is still some myocardial tissue surrounding the defect that is not completely "hardened." This might explain that the 2 patients who failed occlusion at our center experienced dislodgement of the occluder after released. In addition, the defect was generally irregular in shape, largely characterized by multichannel and sieve-like features, which are likely to cause residual shunts. In this context, an occluder with a large size is recommended to fully close the defect as much as possible to reduce the incidence of residual shunts. We used an occluder with a diameter 8−14 mm greater than the defect diameter during the operation and achieved good results.
Procedural complications are known to affect patient prognosis.
We found that patients who developed procedural complications suffered a relatively high mortality rate at 30 days of closure compared to that of patients without complications, but this difference was not The goal of percutaneous closure is to reduce the left-to-right shunt and improve cardiac function. The present work proved the effectiveness of interventional VSR closure in improving cardiac function. Cardiac catheterization and echocardiography data revealed significant reductions in Qp/Qs and PASP after closure and an evident increase in ASP.
In addition, LVEF and LViDd improved to some extent.
The treatments for VSR mainly include conservative treatment using drugs, interventional closure and surgery. The present study focused on the interventional strategy, but there are no relevant studies comparing this approach with drug therapy or surgery, which is a limitation of the study. Additionally, the mechanism of VSR after AMI has rarely been reported. Liu et al. 15 identified multiple risk factors for VSR after AMI, including advanced age, AMI recurrence in the hospital, low systolic blood pressure, lesions in the left anterior descending artery, decreased hemoglobin, low total protein, and high serum magnesium, but further clinical trials are required.
In conclusion, VSR is a life-threatening condition associated with high mortality rates. Our study suggests that percutaneous VSR closure can be a valuable treatment option for suitable patients with VSR after AMI, with the optimal closure time being 3 weeks after AMI. However, increases in CRP and NT-ProBNP should be monitored closely as they are associated with higher risk of death at 30 days after closure.

CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author, [Chuanyu Gao], upon reasonable request.