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Understand the clinical presentation and testing required for diagnosis of paravalvular leak.
Know the indications and contraindications for percutaneous paravalvular leak closure.
Be familiar with interventional techniques and outcomes for percutaneous paravalvular leak closure.
Paravalvular leak (PVL) is a common and underdiagnosed condition affecting both surgical and transcatheter prosthetic heart valves.1–3 Characterised by a gap between the prosthetic valve and the native annular tissue, PVL results in regurgitation of blood from downstream to upstream chamber, occurring most often in conditions of tissue friability such as endocarditis, frailty, corticosteroid use, prior surgical valve replacement and/or in the setting of severe annular calcification. In transcatheter prosthetic valves, PVL occurs due to malapposition of the lower stent frame with the aortic annulus due to various factors including annular calcification, shape mismatch between annulus and prosthesis, prosthesis undersizing, prosthesis malposition or underexpansion.
Although mild PVL is usually asymptomatic, it can occasionally result in clinically significant haemolytic anaemia characterised by the need for blood transfusions, jaundice and/or choluria. More than mild PVL may result in symptoms of heart failure including dyspnoea, fatigue and secondary effects including pulmonary hypertension. In patients receiving transcatheter aortic valve replacement (TAVR), more than mild PVL is independently associated with higher mortality.4 5 The murmur of PVL is often soft in intensity on auscultation and prosthesis shadowing may obscure full detection with transthoracic echocardiography (TTE); for these reasons, a high index of suspicion is required to accurately diagnose PVL. More advanced detailed imaging modalities including transoesophageal echocardiography (TEE) and cardiac CT angiography (CTA) are essential tools to fully evaluate and characterise patients with suspected PVL.
When PVL is believed to be clinically significant, percutaneous PVL closure is indicated to improve quality of life and avoid the need for cardiac surgery.6 Recent studies have shown that successful PVL closure (defined as mild or less residual regurgitation) is also associated with improved survival.7 8 When PVL closure is contraindicated or unsuccessful, cardiac surgery is the treatment of choice in appropriate candidates. This review will detail the contemporary assessment and interventional management of PVL.
PVL: scope of the problem
PVL occurs in 2%–10% of surgical aortic valve replacements and 7%–17% of mitral valve replacements.8 9 In TAVR, PVL of moderate or more severity has steadily declined with improvements in device technology and procedural planning, but still occurs in up to 5% of patients with the latest generation transcatheter valves.
Paravalvular defects are often irregular in shape and can follow a serpiginous track from the downstream to upstream chamber. Up to 5% of cases of PVL may require intervention due to symptoms or haemolytic anaemia. Chronic paravalvular mitral and aortic regurgitation may result in left ventricular (LV) and/or left atrial (LA) volume and/or pressure overload, causing symptoms of heart failure. Due to abnormal compliance of the receiving chamber, the regurgitant volume required to induce symptoms may be relatively modest, leaving standard volumetric measurements of regurgitation severity of limited value. Secondary elevation in pulmonary arterial pressure may result in right-sided heart failure. Paravalvular regurgitation is the most common cause of haemolytic anaemia in patients with prosthetic heart valves. Increased red blood cell shear stress due to turbulent flow through the defect can cause mechanical trauma, fragility and fragmentation of red blood cells. Clinically significant haemolysis tends to be more common in smaller defects with high-velocity jets, in patients with increased red blood cell fragility due to iron and folate deficiency, and in those with pre-existing anaemia due to the increased turbulence occurring from reduced blood viscosity and increased cardiac output. Moderate to severe PVL after both surgical and transcatheter aortic valve replacement is associated with increased mortality.4 10
Diagnostic approach to PVL
All patients with prosthetic heart valves should undergo periodic evaluation with both physical examination and TTE. When PVL is suspected by the development of unexplained heart failure, pulmonary hypertension, haemolytic anaemia, a new murmur on examination or visualisation by TTE, efforts should be undertaken to ensure that the true haemodynamic severity of PVL is known and that the aetiology for PVL is explained as much as possible.11 Endocarditis should always be suspected when new PVL is detected and blood cultures obtained as appropriate. In cases of suspected haemolytic anaemia, complete laboratory testing including peripheral smear, total and direct bilirubin, lactate dehydrogenase and haptoglobin confirm the presence and severity of haemolysis. Given the presence of prosthesis-related acoustic shadowing, PVL may be underestimated or not detected at all by TTE, especially when involving a mitral prosthesis. In most cases of PVL, additional imaging with TEE is required to confirm the presence and severity of PVL and to distinguish from intraprosthetic regurgitation. One exception to the necessity of TEE is in the case of anteriorly located aortic periprosthetic defects which are usually well seen by TTE and are difficult to visualise using TEE due to prosthesis shadowing. Cardiac CTA can be very useful to confirm the diagnosis of PVL, provide information regarding the mechanism, size and location of PVL and for procedural planning of the PVL closure procedure. At our institution, all patients with aortic PVL (either surgical or transcatheter valves) undergo a gated cardiac CTA primarily to aid in procedural planning. In the setting of post-TAVR PVL, cardiac CTA provides important information regarding the transcatheter valve including depth within the annulus and the prosthesis area and expansion. Most cases of PVL are treatable with percutaneous closure; however, contraindications to percutaneous closure include (1) active endocarditis, (2) prosthetic valve thrombosis, (3) unstable prosthesis/rocking motion noted and (4) very large defects comprising >1/3 of the annular circumference. A general approach to interventional management of PVL is outlined in figure 1.
Interventional approach to PVL
The ability to perform successful PVL closure requires a combination of disease-specific medical knowledge and technical skill. A comprehensive understanding of valvular and structural heart disease is necessary to guide appropriate patient selection and thorough procedural planning. Knowledge of abnormal cardiac anatomy and ability to integrate CT, TEE and fluoroscopic images in three dimensions are also critical. Additionally, the interventionalist must have detailed knowledge of the prosthetic valve features including type of prosthesis, radiographic appearance and the presence of other prosthetic valves to facilitate the procedure. Dedicated procedural skills in structural intervention are necessary to gain familiarity with use of multiple complex catheter techniques including transseptal access, LA navigation, wire snaring, LV apical puncture, creation of wire rails and vascular occluder delivery.12 Finally, a comprehensive understanding of the procedural risks and benefits is necessary to facilitate a thorough shared decision-making discussion with the patient.
In patients undergoing aortic PVL closure, conscious sedation may be used as long as prolonged TEE imaging is not anticipated. For mitral paravalvular defect closure, general anaesthesia is usually preferred for patient comfort and safety due to longer procedural time and TEE requirement throughout the procedure for interventional guidance. Fluid communication between the echocardiographer and interventionalist is essential with the use of simple, anatomically based nomenclature to facilitate localisation and crossing of PVLs. Low-resolution biplane fluoroscopy at low frame rates (usually 7.5 frames/s), appropriate collimation and radiation shielding allows for simultaneous orthogonal X-ray plane visualisation, while minimising radiation exposure.
Mitral PVL closure techniques
The preferred technique for mitral PVL closure at our institution is the antegrade transseptal approach with utilisation of either LV anchor wire or an arteriovenous (AV) rail (figure 2).11 13 A 14F sheath is placed in the right femoral vein to minimise blood loss during catheter exchanges. Transseptal LA catheterisation is performed under biplane fluoroscopic and TEE guidance using standard techniques and systemic heparinisation is initiated with frequent assessment of the activated clotting time (we prefer keeping the activated clotting time ≥300 s). Transseptal puncture may be challenging in this population due to distorted cardiac anatomy, septal patching or scarring and the need for more precise localisation of the puncture. Ideally, the puncture is made posterior and near the level of the defect (superior–inferior axis) and in the case of medial defects, posteriorly/inferiorly on the septum to allow room to steer and flex equipment in the LA. For dense fibrotic atrial septal tissue (eg, previous atrial septal repair, multiple previous transseptal cannulations, radiation heart disease and so on), a SafeSept transseptal guidewire (Pressure Products Medical Supplies, San Pedro, California, USA) may aid in obtaining transseptal access owing to the very sharp wire tip and ‘J’ shape that it assumes after crossing the septum, allowing the use of less force and reducing risk of perforation of the opposite wall of the LA. Occasionally, it may be necessary to insert a stiff 0.014 inch wire into the right upper pulmonary vein and balloon dilate the septum in order to allow passage of the steerable left atrial sheath. Radiofrequency and electrocautery are another useful adjunctive tools for obtaining difficult transseptal access.
After transseptal puncture is completed, fluoroscopy gantries are oriented with the right anterior oblique projection showing the mitral prosthesis sewing ring tangentially (on its side and showing tilting discs of a mechanical valve sharply) and the left anterior oblique-caudal view shows the valve en face. These views facilitate three-dimensional navigation and allow immediate detection of valve obstruction (if mechanical prosthesis), as well as recognition of paravalvular versus valvular cannulation when initially crossing the defect. A telescoping coaxial system is introduced into the LA, including a transseptal LA sheath (most commonly an 8.5 French Agilis NxT Steerable Introducer, St. Jude Medical, St. Paul, Minnesota, USA), a 100 cm 6F coronary guide (typically a multipurpose catheter) and a 5F 125 cm multipurpose diagnostic catheter.11 13 Depending on defect location, other curved-tip catheters (such as a JR4) may be used instead. The system can be steered in three dimensions using the deflectable LA sheath allowing the entire mitral valve sewing ring to be probed efficiently. An exchange-length extra support angled hydrophilic 0.035-inch wire (Glidewire, Terumo Medical Corp., Somerset, New Jersey, USA) is passed through the telescoping catheter system with a torque device, allowing the use of finely tuned movements to localise and cross the defect. Occasionally extrasupport 0.017 or 0.14 inch wires can be used for crossing smaller and more serpiginous defects. Three-dimensional TEE allows for localization of the defect sector and visualisation of the wire and catheter. After the wire has crossed the defect, it is looped in the LV and passed through the aortic valve and into the descending thoracic aorta to reduce the risk of losing wire position (provided there is no aortic mechanical prosthesis). After obtaining adequate wire position to provide support, the 5F diagnostic catheter is crossed through the defect, followed by steady advancement of the 6F coronary guide catheter into the LV. These catheters usually cross without the need for excessive force, however if either catheter does not cross, additional techniques may be required, such as guidewire snaring and creation of an arteriovenous (AV) rail to provide more wire support.
The number and size of device occluders to be used is determined through a combination of imaging assessment of the defect dimensions, proximity to the sewing ring, type of prosthesis, the ease with which catheters cross. While small and round defects usually require a single occluder, crescentic or oblong defects are best closed using multiple devices. Very large paravalvular defects occupying up to 25% of the sewing ring are most effectively closed with staggered ‘nesting’ of multiple devices. Bioprosthetic valves typically accommodate a larger device size or number of nested devices due to a lower risk of device interaction with leaflet function. In contrast, the spatial relationship of mechanical prosthesis occluder discs relative to the defect(s) is a key determinant of the size and number of devices that can be implanted without interfering with prosthetic valve function.11 Our preferred device is the Amplatzer Vascular Plug II (AVPII) (St. Jude Medical). The AVPII device is well suited for PVL closure due to its low profile and its fine nitinol mesh construction allowing for deliverability through a variety of catheters. Additionally, it is the lowest cost of the commonly available closure devices. An AVPII of up to 12 mm will fit through a 6F coronary guide catheter without difficulty. When using an anchor wire for anticipated multiple device deployment, a 12 mm AVPII device will fit through a 6F shuttle sheath with an 0.035 inch wire in place. Large devices will require larger size shuttle sheaths. It is important to note that use of this device and others for PVL closure is ‘off-label’ as there is currently no Food and Drug Administration-approved device for this indication. Other devices including the Amplatzer Duct Occluder, Amplatzer Septal Occluder and Amplatzer Muscular VSD Occluder (all manufactured by St. Jude Medical) may also be used. An important caveat is that the nitinol mesh of these devices is stiffer and of larger calibre and is associated with a higher risk of haemolysis.
With single AVPII device placement, the distal third of the occluder is extruded into the LV followed by careful withdrawal of the entire assembly towards the annular plane and mitral valve prosthesis. Continuous assessment of mitral prosthetic leaflet motion should be performed and if there is evidence of impairment, the entire assembly should be readvanced into the LV and alternative strategies should be considered including use of a smaller device or device deployment close to the atrioventricular plane. Once the position of the distal disc is snug against the annular plane, the rest of the device is slowly extruded as the delivery assembly is carefully withdrawn into the LA; depending on the anatomy of the defect the middle disc may be fully expanded (short length defect) or compressed (within the tunnel of the defect).
Aortic PVL closure
Aortic PVL closure is most commonly performed using a retroaortic approach using femoral arterial access (figure 3).11 13 The procedure can often be performed with conscious sedation and TTE used for preassessment and postassessment of aortic regurgitation. When the regurgitation is posterior in location, TEE may be necessary for better visualisation. Depending on the size and number of devices planning to be used for closure, a 6–9F arterial sheath may be placed initially (if more than one AVPII device is anticipated, a larger sheath should be used to allow for haemostasis during catheter exchanges). Defects in the right and non-coronary sinus of Valsalva are cannulated using a 6F 100 cm multipurpose guide with a telescoping 125 cm 5F multipurpose diagnostic catheter. Defects located in the left coronary sinus of Valsalva are often best reached using a 6F AL-1 guide. Using preprocedural cardiac CTA-derived fluoroscopic crossing angles, aortic PVL can often be rapidly crossed using an 0.035 inch angled hydrophilic wire. Once the defect is crossed with the hydrophilic wire and catheter positioned in the LV, the wire can be exchanged for an 0.035 inch Amplatz extra-stiff exchange-length wire with a LV curve. Care should be taken to ensure the catheter and wire are positioned in the apex to optimise support and avoid LV injury during this exchange. Over this wire, a shuttle sheath can then be used to cross the defect. Device size and sequence of deployment are similar as described for mitral PVL closure. Once devices are in place, the degree of aortic regurgitation is assessed using either TEE or using TTE in the setting of predominantly anterior PVL.
In the case of post-TAVR aortic PVL, similar techniques are used with a few important differences. First, it is critical to delineate the mechanism of post-TAVR PVL prior to attempting closure; PVL due to the device being too high or too low in position may not be effectively treated with PVL closure and may require valve-in-valve instead. Additionally, post-TAVR PVL due to an undersized or underexpanded prosthesis may be treatable with balloon postdilatation, especially in the case of multiple circumferential leaks around a balloon-expandable valve.14 In general, paravalvular leaks associated with TAVR are often smaller and more serpiginous compared with surgical valves and may only be crossable with smaller catheters as opposed to coronary guide catheters and shuttle sheaths. In these cases, the AVP-IV devices are optimal choices as they can be delivered through any catheter that accommodates an 0.035 inch wire. Most PVL after TAVR can be successfully closed using the PVL closure techniques described above and typically only require 1–2 devices.14
Outcomes and future directions
The degree of reduction in PVL during the index procedure predicts the amount of symptomatic benefit derived and need for repeat procedures in follow-up after PVL closure.15 16 Recent studies have demonstrated that successful PVL closure defined as mild or less residual regurgitation is associated with improved survival.8 Long-term survival appears to be similar after surgical and transcatheter mitral PVL closure, with a trend towards higher rates of repeat intervention in patients undergoing surgical mitral PVL closure.17 Repeat PVL closure is most commonly required due to the development of new defects and has a similar success rate compared with first time procedures.18 PVL closure after TAVR can also be performed with a similar success rate compared with with surgical aortic prostheses.14 The effectiveness of PVL closure as a treatment for haemolysis is less well understood. Preliminary data suggests that PVL closure is only modestly effective for treatment of haemolysis and seems to be most effective for treating haemolysis associated with mechanical prostheses. Future studies examining the pathophysiology of PVL and factors affecting haemolysis are needed. Additionally, purpose-built devices for PVL closure that may increase the technical success rate are needed.
PVL is a common problem affecting prosthetic heart valves and diagnosis requires careful evaluation. PVL closure is a safe and effective treatment for symptomatic PVL. Successful PVL closure requires an integrated structural heart programme characterised by appropriate patient selection, detailed preprocedural evaluation planning and specialised interventional and cardiac imaging techniques.
Paravalvular regurgitation is a common and underdiagnosed condition.
Detailed imaging modalities including transoesophageal echocardiography and/or cardiac CT are usually required for the assessment of the presence and extent of paravalvular leak.
Indications for percutaneous paravalvular leak closure include the presence of heart failure or haemolytic anaemia attributed to paravalvular leak.
Percutaneous paravalvular leak closure requires specialised interventional and imaging techniques to accomplish successfully.
Successful paravalvular leak closure (defined as mild or less residual regurgitation) is associated with a reduction in heart failure symptoms and improved survival.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
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Provenance and peer review Commissioned; externally peer reviewed.
Author note References which include a * are considered to be key references.
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