Outcomes of a modified approach to transcatheter closure of perimembranous ventricular septal defects

Original Studies

Outcomes of a Modified Approach to TranscatheterClosure of Perimembranous Ventricular Septal Defects

Geri Landman,* MD, Alaina Kipps, MD, Phillip Moore, MD,David Teitel, MD, and Jeffery Meadows, MD

Objectives: To describe the immediate and midterm results of a modified methodfor transcatheter closure of perimembranous ventricular septal defects (pmVSDs).Background: Transcatheter closure of pmVSDs has been associated with developmentof heart block due to impingement on the ventricular conduction system. Ventricularseptal aneurysms (VSAs) are common; the VSA tissue can serve as a target for the de-vice without necessitating direct contact with the conduction system. Methods:Between 2004 and 2011, 15 patients underwent transcatheter closure of a pmVSD uti-lizing a device implanted into a VSA. Catheterization reports were examined in additionto pre-closure, post-closure, and current clinical, ECG, and echocardiographic data.Results: The median age was 20 years (4–61 years), and the most common indicationfor closure was increasing LV dilation. Four different Amplatzer devices were utilized.Following device implantation there was a decrease in Qp:Qs (1.7–1.1) and in RV:LVpressure ratio (0.36–0.31). There were no deaths, no device embolizations, and no newheart block or PR interval prolongation. Three patients developed a new right bundlebranch block (RBBB). The median follow-up time was 1.5 years (4 months to 7.1 years).Two patients required further procedures for important residual shunting. Six continuedto have a “trivial/small” residual leak, but only one had any degree (mild) of residual LVdilation. None of the complications were significantly associated with age or weight atthe time of procedure, original size of the VSD, or size or type of the device used.Conclusion: Transcatheter closure of pmVSD with placement of the device into the VSA issafe and effective, and may result in fewer instances of atrioventricular block and valveabnormalities than have been reported with alternative methods of pmVSD device closure.Persistent VSDs and new RBBBs remain an important issue. VC 2013 Wiley Periodicals, Inc.

Key words: aneurysm; conduction system; atrioventricular block

INTRODUCTION

Transcatheter device closure of perimembranousventricular septal defects has been complicated by theproximity of conduction fibers to the margins of thedefect, resulting in unpredictable episodes of conduc-tion block [1,2]. The mechanism of conduction blockin this setting is likely related to local myocardialinflammation as the most commonly utilized, self-expanding nitinol devices exert expansive force on themargins of the defect. An alternate method of deviceplacement has been described in which the occluderdevice is implanted into the so-called ventricular sep-tum aneurysm (VSA) [3,4]. In this position, the deviceis remote from the conduction system and aortic valve,

but is necessarily integrated into redundant tricuspidvalve tissue, which forms the VSA. It is unknown howwidespread the use of this technique is, though it has

Department of Pediatrics, Division of Pediatric Cardiology,University of California, San Francisco, California

Conflict of interest: Nothing to report.

*Correspondence to: Geri O. Landman, 505 Parnassus Avenue, Box

0632 San Francisco, CA 94143-4144. E-mail: [email protected]

Received 28 July 2012; Revision accepted 2 December 2012

DOI: 10.1002/ccd.24774

Published online in Wiley Online Library (wileyonlinelibrary.com).

VC 2013 Wiley Periodicals, Inc.

Catheterization and Cardiovascular Interventions 00:000–000 (2013)

potential to be used extensively, as VSAs occur in 30–70% of perimembranous ventricular septal defects(pmVSDs) [5,6]. We sought to characterize the proce-dural success and outcomes associated with this alter-native technique of pmVSD closure.

METHODS

A review of the Pediatric Cardiac CatheterizationLaboratory database at the University of California,San Francisco identified all patients who underwenttranscathether closure of a perimembranous ventricularseptal defect (pmVSD) between January 2004 and De-cember 2011. Patients who did not have a ventricularseptal aneurysm associated with the pmVSD wereexcluded. The presence of other cardiac lesions or con-current repair of other defects did not exclude potentialstudy subjects. The study was approved by the Com-mittee on Human Rights at the University of CaliforniaSan Francisco. Patients and referring physicians werecontacted for informed consent and follow-up medicalrecords. All data were collected retrospectively andinterpreted in a non-blinded manner. Cardiac catheteri-zation reports were reviewed for each patient. The clin-ical records, electrocardiograms, and echocardiogramsof these patients were reviewed at three time points foreach patient: prior to procedure, immediately followingprocedure, and most current available.

Definitions

The outcome of VSD closure was defined as suc-cessful if post-procedural echocardiography demon-strated the device in appropriate position with either noresidual or only trivial or small residual shunt acrossthe pmVSD, and the patient did not require any furtherprocedures on the same VSD. VSD closure was classi-fied as unsuccessful if post-procedural echocardiogra-phy demonstrated the device in an inappropriateposition, if there was greater than small residual shunt-ing, or if the patient required an additional procedure,either surgical or transcatheter, to close the remainingVSD. Pre-procedural, post-procedural, and currentmeasurements of the VSD were obtained by 2-D andDoppler echocardiography. The intra-procedural meas-urements of the VSD were all made angiographically.The presence of valvular regurgitation at any timepoint was recorded as an ordinal variable as absent,trivial/mild, moderate, or severe. Similarly, left ventric-ular enlargement was assessed by echocardiographyand was classified as absent, trivial/mild, moderate, orsevere by an experienced echocardiologist. If atrioven-tricular block (AV block) was present, it was classifiedby degree and type. Finally, bundle branch block was

defined as a dichotomous variable, being either presentor absent.

Technical Considerations

Catheterization procedures were performed under ei-ther general anesthesia or conscious sedation as clini-cally indicated. Access was from the femoral vesselsexclusively. Routine anticoagulation was obtained withintravenous unfractionated heparin, with activatedclotting times maintained greater than 260 sec.Approximately 30 min prior to device implantationprophylactic antibiotics were administered, and anadditional dose was given 8 hr later. A routine rightand left heart hemodynamic evaluation was performed.Transesophageal echocardiographic (TEE) imaging wasutilized in all cases in which patients were under gen-eral anesthesia to assess the ventricular septal defectsize, baseline, and changes in valvular competency,and residual shunts after device implantation, whereasintravascular ultrasound was utilized to assess thesevariables when patients were under conscious sedation.The device used to close the pmVSD was chosen atthe discretion of the interventionalist. In each case, thedevice was positioned within the aneurysm of the ven-tricular septum rather than spanning the septal defectitself (Fig. 1A–C). At the conclusion of the procedure,the device was contained within the pouch formed bythe aneurysmal tissue with the goal of occluding allopenings into the right ventricle.

Data Analysis

Data were collected into a standard spreadsheet(Microsoft Excel, Washington) and exported intoSPSS, Version 12.0 (Chicago, IL) for analysis. Cohortdemographic and descriptive variables were summar-ized as means and standard deviations if normally dis-tributed and as medians and ranges if non-normallydistributed. Paired t-tests were used for continuousvariables and McNemar tests were used for binomialvariables to compare consecutive data points for eachpatient (pre-procedure, post-procedure, current). Evalu-ation of unadjusted risk factors for procedure failureand complications was performed using logisticregression.

RESULTS

Patient Demographic and PreproceduralCharacteristics

Fifteen patients underwent cardiac catheterization fordevice closure of a pmVSD using the VSA technique.Patient demographic and pre-procedural characteristicsare provided in Table I. The indication for ventricular

2 Landman et al.

Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).

Fig. 1. Catheterization of the ventricular septal aneurysm. A: Perimembranous VSD with an-eurysm prior to device placement. B: Delivery of Amplatzer vascular plug device into theVSA. C: Delivery of Amplatzer muscular VSD occluder device into the VSA. D: Muscular VSDdevice in place after delivery in the VSA.

TABLE I. Patient Demographic and Pre-Procedural Data, n 5 15

Patient Age

Weight

(kg)

VSD Size

(Angio, mm) Additional Defects Qp:Qs DeviceaHospital

Stay EKG Features

1 39 57 8.5 None 1.0 DO 0

2 20 91 4.5 None 1.8 MVO 1

3 13 48.9 12 None 1.3 DO 1

4 9 19.5 5 None 1.2 VP 1

5 58 90 3.5 None 1.2 DO 1

6 4 14.1 10 None 2.0 MVO 1

7 38 92 14 Bioprosthetic aortic valve 1.7 VP 14 1st degree AV block

8 18 55 5.5 ASD, small PDA 1.6 SO 2

9 17 41 15 ASD 1.8 DO 1

10 7 21 6 ASD 1.7 DO 1

11b 38 145 14.5 None 4.3 SO 1 RBBB

12 33 68.2 9.5 None 1.7 DO 1

13 8 30 14 None 1.2 DO 1

14 46 82 15 None 1.0 DO 1

15b 61 64 10.5 Bioprosthetic aortic valve 1.3 VP 9 RBBB, trifasicular block

Summary

statistics

20 (4–61) 57 (14.1–145) 9.8 6 4.2 ASD 20%; PDA 6.7% 1.7 6 0.8 1 (0–14)

aDO¼Amplatzer Duct Occluder, VP¼Amplatzer Vascular Plug, SO¼Amplatzer Septal Occluder, MVO¼Amplatzer Muscular VSD Occluder.bRequired repeat intervention at a later time point.

Outcomes of a Method for TC Closure of pmVSDs 3


septal defect closure was progressive left ventricularenlargement in all patients. Five patients also hadsymptoms of congestive heart failure. Minor additionalstructural defects were present in three patients (20%),including two with an atrial septal defect and one withan ASD as well as a small patent ductus arteriosus.Two other patients had previously undergone prostheticaortic valve replacement. All patients were in sinusrhythm prior to cardiac catheterization. One patient hadfirst degree AV block at baseline, while two patients’electrocardiograms demonstrated a right bundle branchblock (RBBB), of whom one also had trifasicularblock. Preprocedural echocardiograms were availablefor 14 of 15 patients (93.3%). All patients had somedegree of left ventricular dilation, and 28.6% had mod-erate to severe left ventricular dilation at the time ofthe procedure. Two patients (14.3%) had greater thanmild tricuspid regurgitation, and no patient had greaterthan mild aortic regurgitation.

Procedural Data and Technique

Catheterization procedures for VSD repair were per-formed under general anesthesia in 14 patients andconscious sedation in 1 patient. The technique of VSDclosure, with the exception of placement of the deviceinto the aneurysmal tissue, was not different than innu-merable prior reports and therefore will not be detailedhere. Access was from the femoral vessels in all cases.Three of the patients underwent concurrent proceduresto address other cardiac lesions, including ASD closureand PDA occlusion. The average fluoroscopy time forall patients was 66 min. Excluding those patients withconcurrent interventional procedures, the average fluo-roscopy time was 58 min. The median length of staywas one night with a range of 0–14 nights; the patientwho required 14 days of hospitalization had severalco-morbid medical conditions including severe diabetesand dialysis-dependent renal failure which made hisfluid management challenging to optimize.

Procedural Outcome

Successful VSD closure was obtained with a singledevice in all patients. Eight patients received anAmplatzer Duct Occluder device, three patientsreceived an Amplatzer Vascular Plug, and two patientseach received an Amplatzer Muscular VSD Occluderor Amplatzer Septal Occluder. All patients experiencedhemodynamic improvement (Table II). The averageQp:Qs following device implantation decreased from1.7 to 1.1 (P¼ 0.007), and there was concurrentimprovement in the ratio of right ventricular to leftventricular systolic pressures. No patient experiencedcomplete heart block during the procedure.

Procedural Complications and Re-intervention

There were no deaths or serious intraproceduraladverse events. No patient experienced significantblood loss requiring a transfusion and there were noaccess site complications. There were two repeat inter-ventions. The first occurred in a 38-year-old patientwho despite hemodynamic improvement (a decrease inQp:Qs from 4.3 to 1.5) continued to have significantresidual shunting at the edge of the device and under-went device explantation and surgical VSD closure 5months later. This patient’s data were included in thisanalysis until the time of device explantation. In thesecond patient, echocardiographic assessment the dayafter VSD device closure suggested realignment of thedevice, with exposure of an important residual defect.The device remained stable and patient returned forcardiac catheterization 2 days later where the devicewas repositioned to a more conventional position,involving contact with the crest of the ventricular sep-tum. Because of this, for the purpose of this analysisof the VSA technique, this patient was excluded fromthe analysis after device repositioning. However, it isimportant to note that as a result of the more conven-tional position this patient, who had trifasicular blockpre-repair, experienced complete heart block on post-procedural day 1 following repeat intervention. AVconduction returned with the administration of cortico-steroids; however, the patient underwent elective trans-venous pacer implantation prior to discharge. At lastfollow-up, he remains in sinus rhythm without use ofhis pacer, and he remains with a mild residual VSDwith shunting around the traditionally placed device.

Follow-Up Evaluation

All patients were evaluated prior to discharge withphysical examinations, electrocardiograms, and echo-cardiograms. In addition, all patients and referring pro-viders were contacted for most recent follow-up, which

TABLE II. Cardiac Catheterization Data, n 5 15

Prior to

VSD closure

Following

VSD Closure P

Systemic blood flow (L/min/m2) 4.1 6 1.9 4.2 6 1.8 0.19

Qp:Qs 1.7 6 0.8 1.1 6 0.17 0.01

RV systolic pressure, mm Hg 38 6 21 32 6 11 0.15

LV systolic pressure, mm Hg 91 6 15 101 6 20 0.05

RV:LV pressure ratio 0.36 6 0.11 0.31 6 0.1 0.01

Pulmonary artery pressure, mm Hg 23 6 12 20 68 0.16

Left ventricular end-diastolic

pressure, mm Hg

12 6 6 12 6 6 0.63

Pulmonary capillary wedge

pressure, mm Hg

12 6 7 11 6 7 0.25

RV¼ right ventricular, LV¼ left ventricular.

4 Landman et al.


occurred at a median time of 1.5 years (range: 4months–7.1 years).

Echocardiographic Follow-up

Immediate postprocedural and most recent echocar-diograms were available for all patients. Despite trivialto small residual VSD shunting in eight patients, therewas acute and sustained reduction in left ventricularsize in all patients (Fig. 2). One patient had a transientincrease in tricuspid regurgitation immediately post-procedure, but at most recent follow-up no patient hadgreater than trivial tricuspid regurgitation. There wereno other demonstrable changes in valvular or ventricu-lar function.

Electrocardiographic Follow-up

Prior to device closure, two patients had a RBBBand one patient had minor first degree AV block. Im-mediately postprocedure no patient with a VSA devicesustained complete heart block (upper limit of 95% CI:23%). Three patients developed a new RBBB. At theirmost recent electrocardiographic evaluation, all patientsremained in sinus rhythm, and there was a trend to-ward lower heart rates (P¼ 0.076). There were no newcases of complete AV block. The three cases of RBBBobserved immediately after device placement persisted.

Clinical Follow-up

Ten patients could be contacted by phone; in thecase of young children, parents provided data. Eight often (80%) reported feeling clinically better followingdevice placement. Two patients (20%) described occa-sional palpitations. No patient had experiencedsyncope. One patient, who was less than a month post-

procedure, continued to experience shortness of breathat baseline and with exertion. Subjectively, severalpatients described greater energy, and two parentscommented on their children’s improved growth.

Late Complications and Analysis

Mild device-related hemolysis occurred in onepatient which did not require intervention. One patientwho experienced complete resolution of symptomssubsequently developed intermittent supraventriculartachycardia (SVT) with aberrancy and is now well-controlled in sinus rhythm on beta-blockade. None ofthe complications, including the presence of a residualVSD, were significantly associated with age or weightat the time of procedure, original size of the VSD, orsize or type of the device used.

DISCUSSION

Since the first transcatheter closures of ventricularseptal defects were performed by Lock et al. in 1988[7], transcatheter closure of pmVSD has been associ-ated with several important complications, most nota-bly an unacceptable incidence and timing of completeheart block. Aneursymal transformation of perimem-branous VSDs (so-called ventricular septal aneurysms,VSAs) by integration of ventricular septal and tricuspidvalve tissue occurs in a substantial proportion ofpatients, and can result in complete spontaneous clo-sure. However, when closure is insufficient to mitigatethe hemodynamic burdens of the defect, the VSA tis-sue can serve as a target for transcatheter VSD closurewithout necessitating direct device contact with theconduction system. Our study reports the acute andmidterm results from the first cohort of patients whounderwent transcatheter pmVSD closure exclusively bythis mechanism.

In this cohort, closure of perimembranous VSDsusing the VSA technique was successful in 87% ofcases, which is compatible with more traditional devicetechniques [5,8,9]. All patients experienced immediateand sustained hemodynamic improvement with anacute decrease in Qp:Qs and improvement in left ven-tricular dilation over time, though it should be notedthat for two of the three patients in whom additionalprocedures were performed (ASD and PDA closure),the Qp:Qs ratio was not measured after each individualintervention and the improvement in those patients(1.6–1.1 and 1.8–1.0 respectively) may be in part at-tributable to closure of the additional small defects.However, complete closure of the defect using thistechnique was achieved in only 54% of patients, whichis comparatively low [3,4,8,10–14]. The reasons for

Fig. 2. Frequency and degree of LV dilation as measured byechocardiography pre-procedure and at time of follow-uppost-procedure.



this may be several. First, perimembranous VSDs withVSA formation frequently contain multiple fenestra-tions, and in this setting lower rates of complete clo-sure have been previously described, even usingtraditional methods [9,11]. In addition, it is well knownthat rates of complete closure tend to increase overtime [5,8,9], and it remains possible that several of oursubjects have not been followed sufficiently to observeimprovement in or resolution of shunting; indeed, inthose patients with a “small” residual defect, follow-uptime was less than two months. There is, therefore, rea-son for continued optimism. However, it should beremembered that the presence of a residual shunt inproximity to a device may modify the patient’s risk forendocarditis, and therefore adherence to routine antibi-otic prophylactic protocols is advisable until completeclosure is obtained [15].

None of our patients developed complete AV blockat any point during or following the procedure, withthe illustrative exception of the patient who developedatrioventricular block after he had his device re-posi-tioned in the traditional location during a second proce-dure. Substantially higher rates of AV block have beenobserved with conventional device placement, rangingfrom 1.5% [14] to 22% [16], but averaging 6–10%[12,13]. Several mechanisms have been suggested forinjuring the conduction bundle, including direct me-chanical compression by the device in the immediatesetting and a localized inflammatory reaction in thesubacute setting [17]. By placing the device furtherfrom tissue which is juxtaposed with the AV node, theVSA method may avoid both compressive and inflam-matory forces. However, it is notable that in our studypopulation three patients (20%) developed persistentRBBB, which is considerably higher than the previ-ously described rates of 1.3%–6.2% [4,14,18], althoughOses et al. describe a similar rate of 19.4% [2]. It isplausible that placement of the device within the VSAin the right ventricle may cause compression andinflammation of the right bundle branch more than adevice seated on both sides of the defect. Notably, de-spite placement of the device in this position withinthe redundant tricuspid valve tissue, there was noincrease in tricuspid regurgitation.

Because of the small number of patients in this series,we were unable to predict which patients would developcomplications (bundle branch block or residual shunt)based on identifiable risk factors (age, weight, size ofthe VSD or device, or type of device used). Previousstudies have been mixed on this point; while Buteraet al. found no association between procedural outcomeand the above variables [3], others have reported lowpatient weight as an important risk factor for residualshunts [9] and development of AV block [13].

There are limitations to our study. The patients inour study were larger and older than those reported inprevious series, and the application of this technique tosmaller children requires further investigation. Oursample size was small, and though our average follow-up period was comparable to or longer than other stud-ies of transcatheter closure, it was highly variable. Forsimilar reasons, although we observed no completeheart block, our limited study population set the upperbounds of the 95% confidence interval for this estimateat 23%. From an anatomic perspective the risk forcomplete block utilizing the VSA technique seemscomparatively small, however our observed incidenceof RBBB suggests that interference with the conduc-tion system is not eliminated by this technique. Assuch, larger, longer-term studies are warranted to fur-ther evaluate this method of VSD closure.

CONCLUSIONS

Transcatheter closure of pmVSD with placement ofthe device into the VSA is safe and effective, and mayresult in fewer instances of AV block and valve abnor-malities than have been reported with alternative meth-ods of pmVSD device closure. Small but persistentVSDs and a seemingly increased rate of persistent bun-dle branch blocks remain important issues that warrantfurther evaluation of this method.

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Outcomes of a modified approach to transcatheter closure of perimembranous ventricular septal defects