Review on mitral paravalvular leak: surgical and interventional treatment

Running head: Mitral paravalvular leak closure

Authors

Markus Mach1, MD and Sercan Okutucu2, MD

1 Division of Cardiac Surgery, Medical University Graz, Austria, Heart Team Austria and Karl

Landsteiner Institute for Cardiovascular Research

2 Department of Cardiology, Memorial Ankara Hospital, Ankara, Turkey

Word count of manuscript: 4915 words

Word count of abstract: 125 words

Disclosure: Both authors contributed equally to the paper. Authors have no relationships

relevant to the contents of this paper to disclose.

Corresponding Author

1

Sercan Okutucu, MD, Associate Professor, FESC, FACC, FAHA,

Memorial Ankara Hospital, Department of Cardiology

Cankaya/Ankara P.O: 06520

Phone: +90 312 2536666 (ext.4207) Fax: +90 312 2536623

E-mail: sercanokutucu@yahoo.com

orcid.org/0000-0002-2001-929X

2

Abstract

Paravalvular leak (PVL) is an important complication after surgical valve replacement and might

lead to serious clinical results, including heart failure and/or hemolytic anemia. PVLs are the

result of an incomplete seal between the sewing ring and annulus. It frequently affects surgical

valves in the mitral position, occurring in 5% to 15% of valve replacements. For years, surgery

has been considered the only treatment for symptomatic patients with PVLs. However, surgical

re-intervention for PVLs is associated with a high risk of morbidity and mortality. Therefore,

percutaneous treatment of PVL has become first-line therapy for most patients with symptomatic

PVL. In this review, we will briefly summarize clinical findings, diagnostic modalities,

laboratory assessment, surgical treatment, transcatheter approaches, device choice and outcomes

of interventions in mitral PVLs

Keywords: paravalvular leak, mitral, surgery, intervention, percutaneous

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Introduction

Paravalvular leak (PVL) is defined as regurgitant blood flow through a gap between

surrounding myocardium and a prosthetic heart valve. PVL is a rare but serious complication of

valve replacements, as it increases both morbidity and mortality (1,2). PVLs frequently affects

surgical valves in the mitral position, occurring in 5% to 15% of cases (3). Mitral PVLs is

typically associated with dehiscence of sutures and may result from infection, annular

calcification, friable annular tissue, or technical factors at the time of implantation (4,5).

Until recent decade, surgery has been the available therapy for the treatment of clinically

significant mitral PVLs. However, surgical re-intervention is associated with mortality rates

around 15% with a high rate of PVL recurrence (6,7). Transcatheter PVL closure has emerged as

an alternative to surgical reoperation with first reported case in 2003 using a ductal coil (8).

Since then, various devices have been used with varying degrees of success (6,9-14). Herein, we

performed a literature search and reviewed the diagnostic methods, available devices, surgical

techniques, transcatheter approaches and outcomes for closure of mitral PVLs.

Methods

Search strategy, and data collection

We performed a search of the PubMed database, Scopus, and the Web of Science, using

key words, Mitral [All Fields] AND (paravalvular [All Fields] AND leak [All Fields]) AND

closure [All Fields]” (last update: 21 March 2019). There was no date or language restriction for

our selection of publication. References of selected studies and all abstracts from cardiology

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congresses (American College of Cardiology, American Heart Association, European Society of

Cardiology, Transcatheter Cardiovascular Therapeutics ) were searched for relevant data.

Diagnosis of PVLs

Clinical findings

Although most PVLs are small, remain asymptomatic, and have a benign clinical course,

larger PVLs ends up with serious clinical results such as heart failure (HF) (around 90% of

cases) and/or hemolysis (one third of cases) (15,16). The symptoms are dyspnea, and fatigue

secondary to HF and hemolytic anemia (15-17). Clinically significant PVLs most often occur in

association with mitral prostheses (16). Furthermore, PVL, like any intracardiac defect creating a

significant turbulent flow, is an important pre-existing condition in the context of bacteremia to

develop infective endocarditis (11,18).

Cardiac murmurs when noticed in a patient with prosthetic valve, increases concern

about PVLs. In mitral PVLs, the most prominent finding is a holosystolic murmur heard over the

left sternal border, with radiation dependent on the trajectory of the regurgitant jet (19).

However, auscultation lacks the specificity for diagnosis. Imaging modalities should be

performed to confirm or rule out the presence of PVLs (19,20).

Echocardiographic evaluation of PVLs

The evaluation of PVLs is similar to that used for native valvular regurgitation. However,

it is more challenging and limited by artefacts of the prosthetic valve. This is particularly

difficult during transthoracic echocardiographic evaluation of mechanical mitral prostheses. With

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TEE, the left atrium becomes the near-field chamber and mitral regurgitation can be more readily

evaluated (17,20,21). In order to enable communication between the echocardiographer and the

interventionalist, the location of the dehiscence is best defined in relation to internal landmarks

such as the left atrial appendage and aortic valve. A clock face is often used to describe PVLs

(17)(Figure 1).

Figure 1. Surgical view of mitral PVLs (A), 4-D view of mechanical mitral valve (B).

In assessing mitral PVLs, the area of dehiscence can be detected by transesophageal

echocardiography (TEE) as an area of echo drop-out outside the sewing ring and presence of the

PVL on color-flow imaging. Color-flow imaging is used to localize the PVLs as well as to assess

the severity (Figure 2). The whole sewing ring should be examined carefully by sweeping the

mitral prosthesis from 0° to 180°. Real-time 3D TEE imaging is important for the localization

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and quantification of PVLs. It provides accurate determination of the number and location of

areas of paravalvular dehiscence (17,20-22).

Figure 2. Real-time rendering 4-D echocardiography (A) and color-flow imaging reveal PVL in mechanical mitral valve (shown with arrows).

Commonly used parameters of mitral regurgitation severity in this setting are jet width and jet

area. Although the proximal isovelocity surface area (PISA) approach has not been validated in

the setting of PVL, the presence of a large PISA shell is consistent with more severe

regurgitation. Pulsed Doppler assessment of the pulmonary vein pattern might be useful, and the

detection of systolic retrograde flow is a specific sign of severe mitral regurgitation (17,20,21).

Echocardiographic key criteria for evaluation of mitral prosthetic PVLs are summarized in

Figure 3.

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Figure 3. Echocardiographic key criteria for evaluation of mitral prosthetic PVLs. CMR, cardiac magnetic resonance imaging; CT, computerized tomography; EROA, effective regurgitant orifice area; LV, left ventricle; LVOT, left ventricular outflow tract; MVR, mitral valve replacement; PHT, pressure half time; PVL, paravalvular leak; RF, regurgitant fraction; RVol, regurgitant volume

TEE, especially real-time 3D imaging, is the most useful method for guiding of the procedure. It

is important to avoid misdiagnosing areas of echo drop-out as PVLs. If the dehiscence is large

(>25% of the circumference), a single device is unlikely to be sufficient. Additionally, when the

PVL size is greater than 25% of the circumference, the prosthesis may rock, and it may be

unwise to proceed with device closure because of the high risk of device embolization. Since oral

anticoagulation may have been withheld in these patients, thrombus formation on the prosthetic

valve or within the cardiac chambers and left atrial appendage should be excluded (17,21).

When the antegrade approach is used, TEE may be used to guide the transseptal puncture

and help minimize the risk of inadvertent puncture of surrounding structures. Higher puncture

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allows better access to the lateral mitral annulus. Low-posterior puncture helps accessing medial

parts of mitral valve. TEE also can help guide the passage of the guidewire and catheter through

the PVL. Real-time 3D TEE has been shown to be particularly helpful for passage through

PVLs. TEE helps proper deployment of the PVL closure device. Function of the prosthetic valve

should be assessed to ensure that the PVL occluder does not impede proper opening and closing

of the prosthetic leaflets/discs. With mechanical prosthetic valves, fluoroscopy should also be

used to assess the motion of the leaflets. After release of the device, TEE is performed to assess

residual PVLs. If the residual PVL is severe, placement of additional devices might be

considered (17,21).

Intracardiac echocardiography (ICE) is a unique imaging modality which provides high-

resolution real-time imaging without the requirement for general anesthesia or esophageal

intubation with shorter procedure and fluoroscopic times. Percutaneous PVL closure guided by

ICE is feasible and safe imaging modality which and associated with acceptable procedural

success rates (23).

Other imaging modalities

Cardiac fluoroscopy is useful to monitor and control delivery tools during transcatheter

closure of PVLs. The main disadvantages of fluoroscopy are the inability to determine the 3-D

anatomy of intracardiac tissues and exposure to radiation. Fusion of fluoroscopy and real-time 3-

D TEE is a useful method in catheter-based PVL closure via the transapical approach (24,25).

Angiographic visualization is a useful for diagnosis, define the localization and estimate the size

of PVLs. In case of mitral PVLs, the utility of angiography is less well established; however,

anterolateral PVLs are best approached with fluoroscopy in the posteroanterior view with cranial

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angulation, posteroseptal PVLs in the right anterior view, and lateral PVLs in the lateral view

(26).

Reconstruction with volume rendering of pre-acquired computerized tomography (CT)

angiographic images allows identification of PVLs on the reconstructed image and helps to

identify the best projection to cross the wire (16,27). It is also very useful to identify the apex

and to define the course of the left anterior descending artery in cases of transapical approach.

Magnetic resonance imaging estimates the flow-imaging and volume-based measurements

showing high-grade PVLs. It can accurately assess periprosthetic valve leakage with multiple

regurgitation jets (16).

Laboratory assessment

The turbulent flow caused by the leak around the prosthetic valve is presumed to generate

excessive shearing forces on red blood cells, resulting in intravascular mechanical hemolysis

(24). The hemolysis work-up should also include serum lactate dehydrogenase, haptoglobin, iron

and folic acid levels and peripheral blood smear examination for schistocytes (28).

Treatment algorithms

The indication for reoperation or interventional PVL closure should be made after thorough risk-

benefit evaluation within the institutional Heart Team. As proposed by several working groups,

patients with major prosthetic dehiscence, severe hemolytic anemia, large or multiple PVLs,

concomitant pathologies warranting a surgical intervention and low to moderate surgical risk

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should be referred for surgical treatment, whereas patients with unfavorable surgical anatomy

(porcelain aorta, severe mitral annulus calcification) and high surgical risk should be primarily

treated with an interventional approach (29-31). According to current European guideline

reoperation is recommended if PVL is related to endocarditis or causes hemolysis requiring

repeated blood transfusions or leading to severe symptoms (Class of recommendation I, Level of

evidence C) (32). Transcatheter closure may be considered for PVLs with clinically significant

regurgitation in surgical high-risk patients after Heart Team decision (Class of recommendation

IIb, Level of evidence C) (32). In patients without severe symptoms of HF and absence of

hemolysis strategic observation and interventional risks needs to be weighed against the potential

benefit of early closure (Figure 4).

Figure 4. Treatment algorithm for patients with mitral PVL *Refer to tertiary center if

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institutional experience in PVL treatment is limited. AV, arteriovenous; MVR, mitral valve replacement; PVL, paravalvular leak. [Reproduced with permission from Alkhouli et al.(30)].

Surgical treatment for mitral PVLs

Surgical techniques for mitral PVL closure

Reoperations for PVL closure are commonly performed via conventional median

sternotomy and standard bicaval venous cannulation. Cardioplegia is administered antegrade and

retrograde via cannulation of the coronary sinus. In patients with a history of radiation or bypass

grafts crossing under the sternum right anterolateral thoracotomy in the fourth intercostal space

can be performed with the particular limitation of limited access and sometimes unfeasible cross-

clamping. In these cases, peripheral cannulation and endoclamping, as well as fibrillatory arrest,

can be performed. Various techniques have been established achieving good mitral valve

exposure; however, the standard left atriotomy and the transseptal approach are the most

common access strategies. Exposure can be enhanced by incision of the pericardial reflections

superiorly and inferiorly or transection of the superior vena cava (33).

Assessment of mitral valve function needs to be performed prior to surgery. In case of a

regular mitral valve function and smaller leaks pledgeted suturing may be sufficient and risks

associated with valve replacement can be avoided. Different techniques closing smaller leaks are

described using sutures with pledgets placed either at the atrial or ventricular side of the mitral

valve or even at the right atrial side with the suture passing through the interatrial septum and the

sewing ring of the prosthetic mitral valve (34-36) (Figure 5). Even placing sutures through the

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coronary sinus wall has been described (37). Posterior PVLs can also be closed with pledgeted

sutures passing through the posterior left atrial wall (34). In case of residual PVLs, larger leaks

or fibrotic tethering of the surrounding valve tissue leak closure often requires an (additional)

autologous or bovine pericardial patch (38). In the case of valve dysfunction, dehiscence or

endocarditis valve replacement is necessary. Notably leak recurrence after valve re-replacement

is not uncommon due to annulus damage or calcification impeding adequate suture placement. In

such cases, the new prosthetic valve can be seated within a pericardial skirt sewn to the sewing

ring. While annular patch sutures are placed in a standard fashion through the annulus and the

sewing ring, the pericardial skirt is sutured in a running fashion to the left atrium as additional

sealing (Figure 6).

Figure 5. Transatrial mitral PVL closure: (A) if the leak is located towards the interatrial septum, (B) it can be approached from the right atrial side of the interatrial septum and (C) being aware

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of the location of the conduction bundle and atrioventricular node to provide more secure repair. Another technical strategy for the leak that is located at the aortomitral curtain (D), sutures can be placed through an aortotomy and after retraction of the aortic leaflets (E), the pledgeted sutures pass below the aortic annulus into the mitral prosthesis sewing ring (F) and the pledgets can be seen below the aortic valves cusps (G) [Reproduced with permission from Said et al.(39) ].

Figure 6. Pericardial skirt technique for mitral valve replacement. [Reproduced with permission from Cohn LH. Cardiac Surgery in the Adult. 5th ed. New York: McGraw-Hill, 2016 (33)].

Particular care must be taken during removal of the original (valve) sewing ring not to

resect excessive annular tissue. In case of atrioventricular disruption of the posterior annulus

section pericardial patch repair needs to be performed prior to annular suture placement (40). A

semicircular patch is sewn to the ventricular and atrial pericardium to reconstruct the mitral

annulus (David technique) (41,42). A different technique described by Carpentier uses

atrioventricular figure-of-eight sutures to reconstruct the AV-junction (43). However, care must

be taken for the sutures not cutting through non-compliant ventricular tissue (44). Overly

aggressive bites of annular sutures can injure the circumflex artery and will significantly increase

peri- and postprocedural morbidity and mortality (33). Even though challenging, preservation of

the subvalvular apparatus is also crucial in mitral reoperations. While contractile function is

improved, and posterior annulus disruption is avoided significant improvement in perioperative

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mortality has been shown (45).

Damage extension to the fibrous trigones may require replacement of the mitral as well as

the aortic valve. This usually occurs only in combined aortic and mitral valve endocarditis and

involves replacement of both valves. A pericardial patch can be used for the reconstruction of the

intertrigonal space. The mitral valve prosthesis is secured to the annulus posteriorly, medially,

and laterally as well as superiorly to the patch. The superior part of the patch is also used to

reconstruct the medial aortic annulus where the aortic valve prosthesis is affixed. As perfect

exposure is required for this procedure, an extended transseptal approach or transection of the

superior vena cava and extension of the left atriotomy to the right superior pulmonary vein

toward the dome of the left atrium is performed (44,46). Due to its technical challenge, this

procedure is famously referred to as “Commando procedure” (Figure 7).

Figure 7. The “Commando Procedure”. (A) Division of the superior versa cava facilitates exposure of the structures. (B) The new prosthetic mitral valve is sewn to the annulus but the

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superior portion of the annulus is reconstructed by a pericardial patch that recreates the fibrous trigone. The valve is then sewn to this patch with horizontal mattress sutures.(C) Once the mitral valve prosthesis is in place, the aortic valve prosthesis is secured through-out most of the annulus. The pericardial patch reconstructs the medial part of the aortic valve annulus and the aortic valve is then sewn to the patch. (D) After the valve replacements are complete, the pericardial patch is extended to finish the closure of the aorta and the left atrium [Reproduced with permission from Cohn LH. Cardiac Surgery in the Adult. 5th ed. New York: McGraw-Hill, 2016 (33)].

Outcomes for surgical mitral PVL closure

While a few studies have investigated the outcome of surgical PVL closure in a

heterogeneous cohort of both aortic and mitral cases, only a few have studied the results of

isolated PVL closure in mitral position (29,30,47-50). As many patients referred for this type of

procedure are in NYHA class III or IV (60-80%) due to HF and present frequently present

themselves with hemolytic anemia requiring transfusion (up to 40%) the peri- and postoperative

mortality is significantly increased (29,39,48,51). Up to 3% even depend on mechanical

circulatory support prior to surgery due to cardiogenic shock (39).

Repair has been described to be feasible in up to 76% of cases, whereas replacement was

needed in around 30-50% of all cases (39,48,49,52). For the majority of mitral valve re-

replacements (82%) mechanical valves have been used (39). The risk of in-hospital and early 30-

day mortality is naturally increased as in most redo surgical cases and been described in recent

literature in around 5-30% of treated patients (39,49). Of note, Taramasso et al.(48) observed

significantly higher rates of early mortality after surgical mitral PVL closure than aortic PVL

closure (13% vs. 5%).

While no specific risk factors have been described for early mortality after surgical mitral

PVL repair, residual PVL, reoperation or reintervention due to recurrent PVL, active

endocarditis, chronic steroid use, previous coronary bypass surgery, chronic renal, concomitant

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tricuspid valve surgery, and postoperative dialysis have been described by Said et al. (39) as risk

factors for late mortality after isolated mitral cases. Taramasso et al.(48) on the other hand, found

preoperative chronic renal insufficiency and more than one previous surgery prior to PVL repair

to be predictive parameters for long-term mortality in their combined aortic and mitral cohort. In

the retrospective analysis by Said et al.(39) overall survival at 1, 5- and 15 year after surgical

mitral PVL repair was 83%, 62% and 16% respectively, while Bouhout et al.(52) described in

their study of surgical PVL repair in the aortic and mitral position survival rates of 85%, 73%

and 56% at 1, 5 and 10 years respectively. Equally disappointing long-term outcomes of only

40% of survivors after 12 years have been described in combined aortic and mitral cohorts (48).

Recurrence of PVL after surgical repair or valve replacement in mitral position has been

described in 21%, with reintervention being 6% and reoperation in 9.2% of patients (39).

Notably, no difference in survival and recurrence of PVL has been described between PVL

repair and replacement (39,53).

Outcomes of surgical versus percutaneous mitral PVL closure

Similar to surgical data for mitral PVL repair, most studies compared a heterogeneous

cohort of aortic and mitral PVL patients regarding their either surgical or interventional therapy.

Alkhouli et al.(30) compared surgery to percutaneous mitral PVL closure. This study indicates

more complete occlusion of PVLs in the surgical cohort with the downside of a higher rate of in-

hospital mortality compared to percutaneous repair. However, as typical in such comparisons, an

allocation bias cannot be denied to a certain extent (30,48). Patients referred for surgical repair

are often younger, had a longer time between index surgery and reoperation, and a higher

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prevalence of endocarditis and chronic renal insufficiency. According to Alkhouli et al.(30), risk-

adjusted predictors of in-hospital mortality were chronic renal failure, active endocarditis and

severe mitral annulus calcification. Evaluating completeness of PVL occlusion, surgery has been

demonstrated higher success rates with mild or less residual regurgitation in 92% whereas only

observed in around 70% treated via a percutaneous interventional approach (30).

The difference in repeat intervention or surgery after PVL occlusion in the known

literature is only numerical (11.3% in the interventional cohort vs. 17.2% for surgically treated

patients), however, the time to repeat intervention is significantly shorter in percutaneous cohorts

(about 6 months for interventional treatment vs. 3,5 years for surgical treatment). These findings

are based on the different causes of repeat intervention. While residual PVL and persistent severe

hemolysis are the major drivers for early re-intervention after percutaneous PVL closure,

recurrence of PVL is the leading cause for repeat treatment after surgical closure (30). As already

described for surgical studies, long-term survival after PVL closure in mitral position is

profoundly impaired. Nonetheless, long-term survival after percutaneous PVL closure seems to

be equally limited (30,48,54). As the current trend leads more and more towards interventional

therapy forms, institutional practice patterns may differ due to operator and center experience.

However, a multidisciplinary heart team approach should be mandatory in the treatment of these

complex patients.

Transcatheter techniques

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Mitral percutaneous PVL closure can be performed using the antegrade transfemoral

(venous, transseptal), retrograde transfemoral (arterial), or transapical (TA) access (5). The

procedure is typically performed under general anesthesia using TEE and fluoroscopic guidance.

Antegrade transseptal (TS) approach is generally the first choice for mitral PVL closure.

A lower rather than higher TS puncture is desirable. The angle between the transseptal puncture

and the PVL is important for crossing the defect with the delivery sheath. Steerable sheaths, such

as the Agilis™ sheath (St. Jude Medical, St. Paul, MN, USA), allows to direct the sheath in front

of the PVLs and facilitates wire passage. Usually, a 0.035” hydrophilic wire is used to cross the

PVLs (such as Glidewire®; Terumo Medical Corp., Shibuya, Japan). The hydrophilic wire is

then exchanged for a support wire (such as Back-up Meier™ guidewire; Boston Scientific,

Marlborough, MA, USA)(55). The delivery sheath is then advanced through the defect over the

support guidewire. Radiofrequency (RF) ablation catheters with high steerability such as (RF

Marinr® MR, Medtronic, USA) might be used to cannulate PVLs and advance sheath over the

ablation catheter (Figure 8).

Figure 8. Steerable Agilis™ sheath (St. Jude Medical, St. Paul, MN, USA)(A); cannulation of PVL with RF catheter with high steerability (RF Marinr® MR, Medtronic, USA)(B) and successful closure of the defect (C).

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Placement of delivery catheters sometimes might be challenging especially in serpiginous

and calcific defects. In such instances, transcatheter rails provide greater support, especially

when large sheaths are introduced (9). Following placement of a guidewire across the PVL, the

wire is snared and then exteriorized to provide the operator with both ends of the wire and

greater support for delivery catheter placement (9). Once the delivery sheath is across the defect,

the ventricular part of the device is deployed. The atrial part is then deployed after retracting the

sheath. The efficacy of the implant is controlled by TEE. A “tug test” is performed and free

movement of the prosthetic valve leaflets (in case of a mechanical prosthesis) is confirmed

before device deployment (55). If needed, more than one device can be implanted sequentially.

In the retrograde approach for mitral PVL closure, the defect is crossed with a wire from left

ventricle to the left atrium, and a loop is established. The delivery sheath is advanced over the

loop from the left atrium to the left ventricle through the leak, and the closure device is deployed

(16).

Transapical approach is a good alternative for patients with severe transfemoral access

difficulties, in those where closure is not possible via transfemoral access (54,55). Transapical

access requires general anesthesia, in order to perform a mini-thoracotomy allowing direct

exposure of the left ventricular apex. It is rarely performed by direct apical puncture. To define

the best place for incision or puncture it is advisable to do a CT and coronary angiography to

avoid damage to the coronary arteries. When the left ventricular apex is punctured directly, a

0.018” wire is introduced through the needle and a 5-6 Fr introducer is placed in the LV. With

the help of a Judkins right or a multipurpose catheter and a hydrophilic wire, the leak is crossed,

and the wire is exchanged for a high support 0.035” wire. When the device has been advanced

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through the sheath, the stability of the device has been tested, the prosthesis discs are found to be

functioning well and the flow through the leak has disappeared or decreased sufficiently, the

device is released. the sheath is removed from the muscular apex with self-sealing of the

myocardium (in case of small sheaths) or percutaneous closure of the puncture site by the

implantation of an AMPLATZER Occluder device (usually VSD or a duct occluder)(16,54,55).

Taramasso et al.(54) reported satisfactory acute results of a small series of 17 very high-

risk patients who underwent mitral PVL closure through the transapical route. Notably, 30-day

mortality was 0%, with an acute procedural success of 94%, and these results compared

favorably with open heart surgery. In another series consisting of 43 patients by Ruiz et al. (18)

where the TA access was used for the majority of mitral PVLs, technical success rate for device

deployment in mitral PVLs was 89%. In a retrospective cohort study, Zorinas et al. (25) reported

19 patients underwent surgical transapical catheter-based mitral PVL closure with the Occlutech

PLD Occluder. A reduction of paravalvular regurgitation to a mild or lesser degree was achieved

in 18 (95%) patients. There were no strokes or myocardial infarctions at follow-up. There were

no deaths at 30 days after the procedure (25).

Device choice

The ideal device for PVL closure should be retrievable and repositionable, show good

conformability, have a low-profile deliverability and result in complete sealing after

implantation. A number of AMPLATZER devices which are not specifically designed for PVL

closure have been used. However, most of these devices present several potential limitations.

The only devices specifically dedicated to PVL closure are the crescent-shaped AMPLATZER

Vascular Plug III (AVP III; St. Jude Medical, St. Paul, MN, USA) and Occlutech paravalvular

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leak device (PLD) (Occlutech, Helsingborg, Sweden). The AVP III has an oval shape, multiple

layers, more and thinner wires, smaller pore size, improved surface contact and faster occlusion

compared to other AMPLATZER devices. Due to these characteristics and design, the AVP III is

potentially an ideal device for this procedure and it has recently been used off-label for PVL

closure, mainly in Europe. Nietlispach et al. (12), who described the initial experience with this

device, obtained technical success in 100% of the five patients in whom it was implanted. Cruz-

Gonzalez et al.(56) reported 90.9% success in 33 patients and Smolka et al. (57) reported 93.9%

success in 46 patients. Occlutech PLD is a double-disc device which comes in either a square or

a rectangular shape, one disc being slightly larger than the other. The two discs are connected by

a round or elliptical waist or a small connector. Recently, Occlutech PLD obtained CE approval

for its device specifically designed for PVL closure (58). Table 1 lists the different devices and

their specific features and indications.

Table 1. Different PVL closure devices and their specific features and indications

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ADO, Amplatzer Duct Occluder; ASO, Amplatzer Septal Occluder; AVP, Amplatzer Vascular Plug; PLD, paravalvular leak device; VSD, ventricular septal defect.

Outcomes

Outcomes depends on patient factors, anatomical factors, and on the volume and

experience of the operators (58). García et al. (58) recently assessed the safety and efficacy of

percutaneous closure of PVLs and searched the predictors of procedural success and early

complications. Global technical success of the procedures was 87% and procedural success

occurred in 73% of the patients. Transfemoral access was used in most of the patients (94%) and

the antegrade transseptal approach was used in most of the patients. In multivariate analysis, the

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independent predictors for procedural success in mitral lesions were the type of device used

(AMPLATZER AVP III vs. others, HR 2.68 [1.29-5.54]) and the number of procedures

performed at the centre (top quartile vs. others, HR 1.93 [1.051-3.53])(58).

Alkhouli et al.(59) recently reported procedural success, in hospital outcomes, and

midterm mortality rates in a total of 231 patients underwent percutaneous mitral PVL repair.

Around 70% of patients had mild or no PVL after the procedure. Compared with those who had

more than mild residual PVL, patients with mild or no residual PVL had lower rates of repeat

surgical interventions and lower all-cause mortality. Survival at 3 years was 61% in patients who

had mild or no residual leak and 47% in patients with higher grade of residual PVL. These

findings imply that successful percutaneous PVL closure associates with significant midterm

survival benefit.

In a study reported by Lloyd et al. (60) percutaneous mitral PVL closure was associated

with significant reductions in left atrial and pulmonary arterial pressures and an increase in

cardiac index. They found that higher left atrial pressures during and following percutaneous

mitral PVL closure were independent predictors of poor survival. These findings reflect that

hemodynamic effects might underlie the clinical benefits of PVL closure and might be useful for

intraprocedural guidance.

Millan et al.(61) evaluated the relationship between a successful PVL closure and clinical

outcomes A successful PVL closure was associated with a lower cardiac mortality rate (odds

ratio [OR], 0.08; 95% credible interval [CrI], 0.01-0.90) and with a superior improvement in

functional class or hemolytic anemia, compared with a failed intervention (OR, 9.95; 95% CrI,

2.10-66.73).

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Panaich et al.(62) assessed the effect of percutaneous PVL closure on hemolysis. They found that

percutaneous PVL closure was associated with modest improvement in anemia, blood

transfusion requirements and/or hemolysis markers. This benefit was most significant in patients

with mechanical valves. The degree of residual PVL after closure was not associated with

improvement in hemolytic anemia.

There is usually no complication more than 80% of the cases (58). The most frequent

adverse events are vascular complications and minor bleeding (~8%). Rarely device might be

observed (~3%) successfully snared and retrieved. Pericardial effusion might be detected around

1% of cases. In SpanisH real-wOrld paravalvular LEaks closure (HOLE) registry, the overall

major adverse events rate (death, stroke, and emergency surgery) at 30 days was 5.6%. Similarly,

Sorajja et al.(63) in their initial experience reported a 30-day complication rate of 5.2% (sudden

and unexplained death, 1.7%; stroke, 2.6%; emergency surgery, 0.9%) in 115 patients, and

Calvert et al.(64) described a hospital mortality of 3.9% in 259 patients.

Conclusions

PVL is an important complication after valve replacement and might lead to serious

clinical results, including HF and hemolysis. Multimodality imaging including TEE and cardiac

CT are important in establishing the diagnosis and defining the size, location, and mechanism of

PVL. PVL closure often requires Heart Team approach. Surgery is appropriate for patients with

PVL due to endocarditis or large valve dehiscence. Percutaneous treatment of PVL has

25

significantly less morbidity than redo surgery and should represent the first-line therapy for most

patients with symptomatic PVL. Better dedicated devices and larger case series are needed to

develop these procedures further and improve outcomes.

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