Abstract
Paravalvular regurgitation is a common, potentially life-threatening complication of transcatheter aortic valve replacement. Previous studies report a 65%–94% rate of paravalvular leakage after transcatheter implantation, mostly of mild degree. The rate of significant (≥ + 2) paravalvular regurgitation varies in large clinical trials, and is associated with worse clinical outcome. There is less agreement regarding the significance of mild regurgitation (grade 1 +). There are anatomical and procedural correlates for paravalvular leak—most importantly, severe valve calcification, patient prosthetic mismatch, and device malposition. The following review details the current knowledge on paravalvular regurgitation after transcatheter aortic valve replacement, including diagnosis, correlates, clinical outcome, preventive and therapeutic strategies related to this complication.
1
Introduction
Transcatheter aortic valve replacement (TAVR) has emerged as an alternative therapeutic intervention for patients with severe, symptomatic aortic stenosis who are at high risk for surgical aortic valve replacement (SAVR) . Current evidence suggests that this technique, performed mainly with the Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA) and CoreValve devices (Medtronic, Minneapolis, MN, USA), is feasible and provides clinical improvement and superior hemodynamic performance compared to surgical bioprothesis . Nevertheless, there are some concerns regarding safety aspects of the procedure. Paravalvular leakage (PVL) is occasionally identified as a major procedural complication and could be viewed as a limitation of TAVR. This review aims to describe the current knowledge on paravalvular regurgitation after TAVR, namely, its incidence, correlates, clinical significance, and available treatment approaches for this complication.
2
Mechanism of PVL
During SAVR, the heavily calcified valve is initially excised and a new prosthesis is sutured directly to the aortic annulus. Incomplete seal between the round sewing ring and the annulus can occur since the space created after removing the calcified tissue is not circular. PVL after surgery may also occur when ≥ 1 annular sutures have pulled out. However, in open heart surgery, there is much more control when sealing potential culprit areas for PVL.
With percutaneous valve implantation, the mechanism of PVL is profoundly different from that of SAVR for two main reasons: (1) no decalcification is performed; and (2) the valve is implanted without suturing. With this technique, the stent-mounted prosthesis is initially compressed against the aortic annulus followed by positioning and expansion. The disrupted calcium may prevent full and symmetric prosthesis expansion, thereby reducing strut apposition and in extreme cases perforating the sealing skirt. This process might lead to a lack of congruence between the annulus and implanted device, which may result in PVL. The height of the implanted device skirt may play an important role in this context as well, whereas long skirts may diminish PVL.
2
Mechanism of PVL
During SAVR, the heavily calcified valve is initially excised and a new prosthesis is sutured directly to the aortic annulus. Incomplete seal between the round sewing ring and the annulus can occur since the space created after removing the calcified tissue is not circular. PVL after surgery may also occur when ≥ 1 annular sutures have pulled out. However, in open heart surgery, there is much more control when sealing potential culprit areas for PVL.
With percutaneous valve implantation, the mechanism of PVL is profoundly different from that of SAVR for two main reasons: (1) no decalcification is performed; and (2) the valve is implanted without suturing. With this technique, the stent-mounted prosthesis is initially compressed against the aortic annulus followed by positioning and expansion. The disrupted calcium may prevent full and symmetric prosthesis expansion, thereby reducing strut apposition and in extreme cases perforating the sealing skirt. This process might lead to a lack of congruence between the annulus and implanted device, which may result in PVL. The height of the implanted device skirt may play an important role in this context as well, whereas long skirts may diminish PVL.
3
Diagnosis of PVL
Assessment of PVL severity after valve implantation is challenging, and determination of the precise grading of the regurgitation is controversial . The evaluation should take place both during the procedure and at follow-up ( Table 1 ). The regurgitating jet is three-dimensional in nature, commonly eccentric, and entrained along the ventricular wall, especially in those developing after TAVR . The severity of PVL can be assessed by evaluating patient hemodynamics, echocardiography, aortography, and cardiac magnetic resonance (CMR) imaging. The process of diagnosing and grading PVL after TAVR should be integrative, using a combination of qualitative and quantitative parameters acquired from different modalities. In cases with a discrepancy in the results, an explanation should be determined and final diagnosis should be based on the most reliable evaluation.
| During the index procedure |
| Invasive hemodynamic assessment a |
| Aortography |
| Echocardiography b |
| Post-procedure |
| Physical examination |
| Echocardiography b |
| Cardiac magnetic resonance |
a Including direct assessment of left ventricular end-diastolic pressure.
3.1
Hemodynamic evaluation
Clues for acute aortic regurgitation include the following: tachycardia; elevation of the left ventricular end-diastolic pressure; decrease in systemic diastolic pressure (equalization of end-diastolic aortic and left ventricular pressures); absence of a “dicrotic notch” on aortic pressure tracing; and premature mitral valve closure according to simultaneous pressure tracing of the pulmonary capillary wedge and the left ventricle . Recently, a quantified index of aortic regurgitation severity (AR index) was described: the end-diastolic gradient across the aortic valve (aortic pressure − left ventricle pressure) divided by the systolic blood pressure × 100 . An index < 25 was associated with higher 1-year mortality ( Fig. 1 A, B ).
3.2
Echocardiography
Although severity of PVL is commonly evaluated by echocardiography, inherent limitations of ultrasound imaging make precise characterization and quantification of PVL magnitude difficult, which may lead to underestimation of regurgitant flow . Echocardiographic parameters used to evaluate the severity of aortic regurgitation mainly include jet length and area, deceleration of the Doppler wave measured as pressure half-time, and aortic reversal of flow ( Fig. 2 ). Severe regurgitation is usually diagnosed when regurgitant volume is ≥ 60 cc/beat or regurgitant fraction is ≥ 50%. The recently published Valve Academic Research Consortium (VARC) II definitions suggested several such semi-quantitative and quantitative parameters for the diagnosis of severe PVL after TAVR . Transesophageal echocardiography (TEE) could improve imaging of the implanted valve and evaluation of its function and therefore should be performed when PVL severity is in doubt . TEE is especially helpful in evaluating PVL in cases with technically difficult transthoracic imaging and is able to exactly delineate the location and mechanism of the leak. The long-axis view is useful for measuring jet width and its relation to outflow tract. In Placement of AoRTic TraNscathetER Valve Trial (PARTNER), a method for defining the degree of PVL was based on parasternal short axis view and the jet arch length in relation to the aortic valve annulus: no PVL (no regurgitant color flow), mild (arch length < 10%), moderate (10%–30%), and severe (> 30%). TEE may be limited when evaluating PVL in the mid-esophageal level because of acoustic shadowing. In some cases it is critical to evaluate the device from the trans-gastric view. Three-dimensional TEE, although evaluated mostly in screening patients for TAVR, seems a promising tool in evaluating PVL severity and should be studied more in the future.
3.3
Aortography
Aortographic contrast injection has long been used for the assessment of aortic regurgitation severity . This technique, although sensitive, is subjective and semi-quantitative. Moreover, it is almost impossible to differentiate intravalvular regurgitation from PVL by aortographic evaluation only. There are several rules to follow in order to correctly assess PVL severity by aortography: The pigtail should be positioned only slightly above the functioning position of the implanted valve; ≥ 20 mL of contrast should be injected; and rate of injection should be ≥ 16 cc/s at 1000–1200 lb/in 2 . Image projection should well visualize the proximal aorta, as well as the entire left ventricle, in order to best evaluate for blood regurgitation into the left ventricle. Some operators advocate using the right anterior oblique projection for this evaluation. A scale of 1 + to 4 + is usually used: mild regurgitation (1 +) when only a small amount of contrast enters the left ventricle and does not fill the chamber; moderate regurgitation (2 +) when the contrast faintly fills the entire ventricle and does not clear rapidly; moderate–severe (3 +) when ventricle opacification is equal in density to the ascending aorta; and severe (4 +) when ventricle opacification is greater than in the aorta .
3.4
Magnetic resonance
CMR imaging is a promising new tool for measuring volume of cardiac chambers and blood flow, and may accurately assess aortic regurgitation severity . Sherif et al. evaluated PVL in a small group of patients who underwent CoreValve implantation using aortography, echocardiography and CMR, and found a significant agreement between CMR imaging analysis and aortographic assessment. None of these evaluations were in agreement with the echocardiographic results. It was evident that echocardiography underestimated the degree of regurgitation especially of eccentric jets; and CMR, with its volumetric imaging, probably improved analysis accuracy. CMR will not soon replace echocardiography as the main modality for PVL assessment, especially during a procedure or as an acute bedside modality. However, CMR may play a role after TAVR in patients with a discrepancy between clinical manifestation (suggesting severe PVL) and echocardiographic signs (mild PVL).
4
Incidence of PVL
Since the diagnosis of PVL severity is complex and mostly subjective, it is difficult to precisely define the incidence of significant PVL after TAVR; in studies there is a wide variability of PVL rates after procedures.
After SAVR, the incidence of PVL of any significance is 10%–48%, is mostly mild, and has a benign course . In a recent evaluation of 3201 patients who underwent SAVR, 4.2% had ≥ 2 + PVL . In the surgical arm of the PARTNER Cohort A trial, ≥ 2 + PVL was noticed in only 0.9% of cases 30 days after the procedure and in 1.9% of cases after 1 year .
The incidence of PVL after TAVR is much higher than after surgery. Preliminary studies using the Edwards SAPIEN device reported a 65%–94% rate of any PVL, mostly of mild degree . The rate of significant PVL in large clinical trials is summarized in Table 2 . The rate of significant ≥ 2 + PVL is 1.9%–47% after Edwards SAPIEN implantation . In the PARTNER trial, the only published study using Core Lab evaluation of echo data, the rate of ≥ 2 + PVL 30 days after the procedure was 12.2% in cohort A and 11.8% in cohort B . The SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry analysis of 1038 patients revealed a ≥ 2 + PVL rate of only 1.9%: 1.5% in the transfemoral cohort and 2.3% in the transapical cohort . After CoreValve device implantation, the incidence of ≥ 2 + PVL was reported as 17.3%–21% . Nuis et al. reported ≥ 3 + PVL in 13% of patients while Tamburino et al. evaluated 663 patients undergoing CoreValve implantation and revealed a 21% PVL rate.
| Number of patients | Early post-procedure paravalvular leakage incidence | Remarks | |||
|---|---|---|---|---|---|
| No | < Moderate | ≥ Moderate | |||
| SAVR | |||||
| Sponga et al. | 3201 | 4.1% | |||
| PARTNER Cohort A | 351 | 0.9% | 1-year incidence: 1.9% | ||
| Rallidis et al. | 84 | 57.1% | 38.1% | 4.8% | |
| O’Rourke et al. | 608 | 82.9% | |||
| Ionescu et al. | 270 | 94% | |||
| TAVR: Edwards SAPIEN | |||||
| PARTNER Cohort B | 179 | 11.8% | 1-year incidence: 10.5% | ||
| PARTNER Cohort A | 348 | 12.2% | 1-year incidence: 6.8% | ||
| SOURCE registry | 1038 | 1.9% | Transfemoral: 2.3%; transapical: 1.5% | ||
| TAVR: CoreValve | |||||
| Tamburino et al. | 663 | 21% | Increased late mortality for ≥ moderate PVL with odds ratio of 5.5 | ||
| Buellesfeld et al. | 126 | 42% | 52% | 6% | 2-year incidence: no: 63%; mild: 37% |
| Takagi et al. | 79 | 26.6% | 53.1% | 20.3% | 6-month incidence: no: 24.4%; mild: 48.8%; moderate: 26.8% |
| Nuis et al. | 150 | 13% | |||
| TAVR: combined Edwards SAPIEN and CoreValve | |||||
| French registry | 3195 (Edwards SAPIEN: 2107; CoreValve: 1043) | 37.8% | 45.7% | 16.5% | CoreValve: ≥ moderate in 21.5%; Edwards SAPIEN: ≥ moderate in 13.9% |
| UK registry | 870 (CoreValve: 452; Edwards SAPIEN: 418) | 39% | 47.4% | 13.6% | CoreValve: ≥ moderate in 17.3%; Edwards SAPIEN: ≥ moderate in 9.6% |
| German registry | 690 (CoreValve: 582; Edwards SAPIEN: 108) | 27.7% | 55.1% | 17.2% | CoreValve: ≥ moderate in 17.9%; Edwards SAPIEN: ≥ moderate in 13.9% |
| Zahn et al. | 697 (CoreValve: 109; Edwards SAPIEN: 588) | 27.6% | 54.9% | 17.5% | |
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