A Case of Hemolysis after Percutaneous Ventricular Septal Defect
Closure with a Device

Hemolytic anemia related to intracardiac prosthetic materials is well recognized. It was first reported by Sayed et al, when a Teflon ASD patch produced intravascular hemolysis.¹ Since then, intravascular hemolysis has been described after postoperative interventions, including both mechanical and biological prostheses.^2–7 Recently, hemolysis has been reported following transcatheter closure and occlusion of patent ductus arteriosus (PDA),^8,9 as well as after coil embolization.^10–13 We describe intervascular hemolysis caused by an Amplatzer muscular ventricular septal defect (VSD) closure.

Case Report. A 74-year-old female with a history of hypertrophic obstructive cardiomyopathy and New York Heart Association class III dyspnea was noted to have a lifelong murmur. She described a 3-year history of progressive dyspnea, chest pain and presyncope, with an effort tolerance of 100 feet. Physical examination revealed a regular heart rate of 60 beats per minute, and blood pressure of 140/60 in the sitting position. There was no elevation of the neck veins, but a positive hepatojugular reflex was present. A hyperdynamic, undisplaced apical impulse and palpable S4 were noted. A grade II-III/VI late-peaking systolic murmur was noted. Lung fields were clear and abdomen and extremities were unremarkable. A chest X-ray showed normal heart size. Electrocardiography showed significant left ventricular hypertrophy (LVH).

A transthoracic echocardiogram (TTE) revealed typical features of hypertrophic obstructive cardiomyopathy, with a 100 mmHg gradient in the left ventricular outflow tract (LVOT) at rest, systolic anterior motion, and mild mitral regurgitation. With exercise, the LVOT gradient increased to 130 mmHg. Coronary angiography showed no significant coronary artery disease.

The patient underwent surgery with a septal myotomy-myectomy to relieve the obstruction. Intraoperatively, an iatrogenic VSD was noted and a pericardial patch repair completed. Postprocedure, a small left-to-right shunt was noted.

Eight months later, the patient returned with worsening exertional dyspnea, ascites and edema. TTE revealed partial dehiscence of the ventricular septal defect patch repair and a pulmonary artery (PA) systolic pressure estimated to be 90 mmHg.

Despite medical management, she continued to have New York Heart Association class III symptoms. An echocardiogram revealed diastolic right-to-left shunting through the VSD with inspiration and a high-velocity jet through the ventricular septal defect. The patient and her family were reluctant to proceed with open-heart surgical management. Therefore, transcatheter closure was offered to close the VSD. At cardiac catheterization, left ventriculography revealed a residual large left-to-right shunt at the lower patch margin. A sizing balloon identified the stretch diameter of the VSD, which was then used to identify the size of the occluder needed. The patient underwent percutaneous placement of an 18 mm muscular VSD occluder device, with trivial residual shunt after the procedure.

At follow up, she developed anemia refractory to medical treatment and required multiple blood transfusions, which increased in frequency over a 2-month period. She had no signs of bleeding and no melena. Echocardiography revealed a right ventricular systolic pressure of 65–70 mmHg, normal left ventricular (LV) size and systolic function, and moderate aortic regurgitation. Unfortunately, a new high-velocity left-to-right shunt was noted through the VSD closure device. Laboratory data showed a positive D-dimer, a positive soluble complex fibrin monomer, and hemoglobin of 8.6. A peripheral smear showed features consistent with intravascular hemolysis. Blood antibody tests excluded an immune or drug-induced mechanism of hemolysis. It was felt that the intravascular hemolysis was due to blood flow from left to right at a high velocity through the Amplatzer device.

Right heart catheterization revealed an elevated pulmonary artery (PA) wedge pressure, and the right ventricular pressure was estimated at 5^1/4 mmHg. A step-up in oxygenation from the right atrium to the right ventricle from 53% to 80% was noted. A Qp/Qs of 2.1 was calculated. A left ventriculogram again revealed shunting across the VSD that was consistent with shunting through the Amplatzer device.

In light of these findings, the patient underwent surgical removal of the Amplatzer device, with concomitant VSD patchclosure and aortic valve repair without complication. Complete symptom resolution with no evidence of hemolysis was observed postoperatively and at 3-year follow up.

Discussion. Congenital VSDs have been repaired using percutaneous approaches for several years. This experience has led to attempts at reproducing this technique in postinfarction septal defects and iatrogenic traumatic VSDs. This case illustrates the utility of percutaneous closure of traumatic VSDs when reoperation is contraindicated, either due to patient factors or if the risk is considered excessive. To our knowledge, this is the first reported case of intravascular hemolysis due to a VSD closure device requiring surgical removal. Intravascular hemolysis secondary to mechanical and bioprosthetic valves and PDA closure devices have been well described in the literature.^8,9,14

Experience with post-myocardial infarction VSD closure devices is limited to 2 case series, each reporting 18 cases.^15,16 The first experience by Landzberg and Lock¹⁵ involved a singlecenter experience of percutaneous closure of postinfarction VSDs using the older closure devices (the Clamshell double umbrella and the CardioSEAL). They reported successful deployment of the device in 17 of 18 patients. The second case series was from the multicenter U.S. registry of transcatheter closure of postinfarction VSDs.¹⁶ The Amplatzer muscular VSD device (PIMVSD) was used. Successful deployment was found in 16 of 18 (89%) of the cases, and a 30-day mortality of 28% was reported.

Complications of the procedure were uncommon in both series. The U.S. registry reported 2 patients with intraprocedural blood loss requiring transfusions, 2 patients with bradycardia and another with transient LV dysfunction. Landzberg and Lock reported 4 patients with intraprocedural blood loss requiring transfusions and 1 patient with transient self-limited hemolysis. Hematomas, intraprocedural bradycardia and 1 patient with worsening LV function were all described. No long-term sequelae were reported in either series. Intravascular hemolysis after using the VSD closure device is a known potential complication. It has been described as only transient, and rarely requires transfusion. After reviewing the literature, there have been only a few reports of VSD closure deviceinduced refractory intravascular hemolysis. Chessa et al¹⁷ reported 2 patients with hemolysis in their experience with muscular VSD closure. One of these patients died within 3 days after device placement. Our patient represents a chronic hemolysis with documented hemolysis through the waist of the device. This is an important distinction for the management of the patient.

The Amplatzer muscular VSD device (AGA Medical Corporation, Golden Valley, Minnesota) (Figure 1) is a nitinol construct with a short connecting waist corresponding to the size of the VSD. Amplatzer devices are self-centering and the discs and waist are filled with polyester patches. The patches improve device closure, which occurs via in situ thrombosis. In addition, Amplatzer devices are retrievable after deployment for repositioning, if the initial result is unsatisfactory. They are not retrievable, however, once the procedure is completed.

The mechanism of intravascular hemolysis due to intracardiac mechanical devices with high flow is well described. Rapid acceleration, fragmentation and collision of high-velocity blood are associated with a high shear stress that leads to hemolysis. In mitral valve prosthesis-induced hemolysis, a fluid dynamic simulation model identified distinct patterns of regurgitant flow that were associated with high shear stress, and therefore were thought to be the etiology of the hemolysis.¹⁸

Hemolysis after percutaneous closure of PDAs is associated with the presence of residual ductal flow.¹⁹ The likely mechanism of hemolysis is high-velocity turbulent blood flow past the ductal device, leading to mechanical fragmentation of erythrocytes.²⁰ There is 1 case report of an adult patient with a PDA who developed severe intravascular hemolysis after ductal occluder deployment related to shunting through the middle of the device. However, there are no reported cases of persistent hemolysis after VSD occluder deployment that required device removal. This report represents the index case of hemolytic anemia requiring surgical removal of a VSD closure device.

Conclusion. Percutaneous closure of VSDs has been used for many years for congenital VSDs. Recently, its utility in postinfarction VSD closure has been shown. We illustrate the role of percutaneous closure to repair traumatic VSDs that occur during surgery. Compared with surgical closure of the VSD, percutaneous transcatheter closure carries a lower rate of morbidity and mortality. Complications with this technique are uncommon. We describe refractory intravascular hemolysis due to a VSD closure device, a rare complication of device placement.

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