Impact of Over-Expansion on SAPIEN 3 Transcatheter Heart Valve Pericardial Leaflets

Self-Expanding Versus Balloon-Expandable Valve: Are We at the Cusp of Delivering a Perfect Transcatheter Aortic Valve?

Senile calcific aortic stenosis (AS) is the most common acquired valvular heart disease with an increasing prevalence attributable to an aging population. Survival is poor in patients with severe or critical AS, chiefly after the onset of symptomology that primarily includes angina, dyspnea, or syncope. On the onset of symptoms, mortality occurs at very high rates during the ensuing 2 to 3 years.1 Until recently, surgical aortic valve replacement represented the sole therapy that definitive reduced mortality and morbidity in patients with severe symptomatic AS, with medical therapy generally ineffective of these patients. Given the advanced age commonly associated with severe AS, a high proportion of these patients are denied surgical intervention because of multiple comorbidities and excessively high surgical risk.2 Recently, transcatheter aortic valve replacement (TAVR) has emerged as a novel disruptive technology that serves an alternative therapy to surgical AVR and has been shown to be an effective therapy in nonoperable and high-risk patients with severe symptomatic AS.3,4 TAVR was first described in humans by Cribier et al in 20025 by a transvenous approach delivered in an antegrade fashion. This technique requires a transseptal puncture and passage of the aortic stent valve across the mitral valve to the aortic position. Subsequently, array of alternative transvascular approaches have arisen, including transfemoral, transaortic, trans-subclavian, and aortic methods. Of these, the retrograde transarterial approach through the femoral artery, developed by Webb et al,6 has been the commonly used approach, with >60 000 such procedures performed worldwide to date. To date, the global experience with TAVR as documented in both single and multicenter registries as well as through multicenter trials have shown good clinical outcomes with improvement in hemodynamic and clinical status, establishing TAVR to be a feasible alternative therapy to traditional surgical aortic valve …

Requiem for Routine Self-Expanding TAVR Valves? A Commentary on the Comparative Analysis of Evolut PRO Versus Sapien Ultra Valves for Transfemoral Transcatheter Aortic Valve Implantation Registry (OPERA-TAVI)

Failed bioprosthetic valve approaches: Transcatheter aortic valve replacement approach

INTENTIONAL UNDEREXPANSION OF BALLOON EXPANDABLE TRANSCATHETER HEART VALVES DURING TRANSCATHETER AORTIC VALVE REPLACEMENT - 12 MONTH FOLLOW-UP

On 16 April 2002, my colleagues and I performed, in an inoperable and desperately ill man with critical calcific aortic stenosis (AS), the first clinical percutaneous implantation of an aortic valve bioprosthesis. As of 2013, more than 80,000 patients have been treated; and transcatheter aortic valve replacement (TAVR), so strongly criticized by all the experts throughout the early years, continues to grow in parallel with its constant technological improvements. Transcatheter aortic valve replacement can now be recognized as a medical breakthrough. It is a revolutionary technology that meets an unfulfilled clinical need for a common disease, is validated by rigorous evidence-based studies, and is applicable worldwide. We report here the main phases of this 20-year odyssey and briefly consider the prospects of TAVR, which remains in continuous development.

Limitations of Transcatheter Heart Valve Replacement Depth Assessment by Invasive Angiography—a Multi-Detector Computed Tomography Analysis

Bioprosthetic valve fracture (BVF) can be used to improve transcatheter heart valve (THV) haemodynamics following a valve-in-valve (ViV) intervention. However, whether BVF should be performed before or after THV deployment and the implications on durability are unknown. Aims: We sought to assess the impact of BVF timing on long-term THV durability. The impact of BVF timing was assessed using small ACURATE neo (ACn) or 23 mm SAPIEN 3 (S3) THV deployed in 21 mm Mitroflow valves compared to no-BVF controls. Valves underwent accelerated wear testing up to 200 million (M) cycles (equivalent to 5 years). At 200M cycles, THV were evaluated by hydrodynamic testing, second-harmonic generation (SHG) microscopy, scanning electron microscopy (SEM) and histology. At 200M cycles, the regurgitant fraction (RF) and effective orifice area (EOA) for the ACn were 8.03±0.30%/1.74±0.01 cm2 (no BVF), 12.48±0.70%/1.97±0.02 cm2 (BVF before ViV) and 9.29±0.38%/2.21±0.0 cm2 (BVF after ViV), respectively. For the S3 these values were 2.63±0.51%/1.26±0.01 cm2, 2.03±0.42%/1.65±0.01 cm2, and 1.62±0.38%/2.22±0.01 cm2, respectively. Further, SHG and SEM revealed a higher degree of superficial leaflet damage when BVF was performed after ViV for the ACn and S3. However, the histological analysis revealed significantly less damage, as determined by matrix density analysis, through the entire leaflet thickness when BVF was performed after ViV with the S3 and a similar but non-significant trend with the ACn. Conclusions: BVF performed after ViV appears to offer superior long-term EOA without increased RF. Ultrastructure leaflet analysis reveals that the timing of BVF can differentially impact leaflets, with more superficial damage but greater preservation of overall leaflet structure when BVF is performed after ViV.

Balloon-Expandable Valve Geometry After Transcatheter Aortic Valve Replacement in Low-Risk Patients With Bicuspid Versus Tricuspid Aortic Stenosis

Coronary access (CA) after transcatheter aortic valve replacement (TAVR) with supra-annular transcatheter heart valves (THV) can be challenging. Specific Evolut R/Pro and Acurate Neo THVs orientations are associated with reduced neo-commissure overlap with coronary ostia, while SAPIEN 3 THV cannot be oriented. With the ALIGN-ACCESS study (TAVR With Commissural Alignment Followed by Coronary Access), we investigated the impact of commissural alignment on the feasibility of CA after TAVR. We performed coronary angiography after TAVR with intra-annular SAPIEN 3, supra-annular Evolut R/Pro, and Acurate Neo THVs in 206 patients. Evolut THVs were implanted aiming for commissure alignment. Alignment of Acurate Neo was retrospectively assessed in 36, intentionally attempted in 26 cases. The primary end point was the rate of unfeasible and nonselective CA after TAVR. Thirty-eight percent of patients received SAPIEN 3, 31.1% Evolut Pro/R, 30.1% Acurate Neo THV. Final valve orientation was favorable to commissural alignment in 85.9% of Evolut and 69.4% of Acurate Neo cases (with intentional alignment successful in 88.5%). Selective CA was higher for SAPIEN 3 than for aligned and misaligned supra-annular THVs (95% versus 71% versus 46%, P<0.001). Cannulation of at least one coronary was unfeasible with 11% misaligned supra-annular, 3% aligned supra-annular, and 0% SAPIEN 3 THVs. Independent predictors of unfeasible/nonselective CA were implantation of a misaligned supra-annular THV (odds ratio, 4.59 [95% CI, 1.81-11.61]; P<0.01), sinus of Valsalva height (odds ratio, 0.83 [95% CI, 0.7-0.98]; P=0.03), and THV-sinus of Valsalva relation (odds ratio, 1.06 [95% CI, 1.02-1.1]; P<0.01). Commissural alignment improves the rate of selective CA after TAVR with supra-annular THVs. Nevertheless, aligned supra-annular THVs carry higher risk of unfeasible/nonselective CA than SAPIEN 3. Patients with a misaligned supra-annular THV, low sinus of Valsalva, and higher THV-sinus of Valsalva relation are at highest risk of impaired CA after TAVR.

Prior studies in patients with transcatheter aortic valve implantation (TAVI) demonstrated an influence of transcatheter heart valve (THV) position on the occurrence of new conductions disturbances (CD) and paravalvular leakage (PVL) post TAVI in balloon-expandable valves (BEV). Purpose of this study was to investigate the THV implantation depth and its influence on the occurrence of CD and PVL in self-expanding valves (SEV). We performed fusion imaging of pre- and post-procedural computed tomography angiography in 104 TAVI-patients (all with Evolut R) to receive a 3-D reconstruction of the THV within the native annulus region. The THV length below the native annulus was measured for assessment of implantation depth. Electrocardiograms pre-discharge were assessed for conduction disturbances (CD), PVL was determined in transthoracic echocardiography. The mean implantation depth of the THV in the whole cohort was 4.3 ± 3.0 mm. Using the best cut-off of ≥ 4 mm in receiver operating characteristic curve analysis (sensitivity 83.3%, specificity 60.0%) patients with lower THV position developed more new CD after TAVI (68.2 vs. 23.7%, P < 0.001). A deep THV position was identified as the only predictor for new CD after TAVI (odds ratio [CI] 1.312[1.119–1.539], P = 0.001). The implantation depth showed no influence on the grade of PVL (r = 0.052, P = 0.598). In patients with TAVI using the Evolut R SEV, a lower THV positioning (≥ 4 mm length below annulus) was a predictor for new conduction disturbances. In contrast, implantation depth was not associated with the extent of PVL.Graphic abstractProstheses positions of self-expanding valves and their influence on the occurrence of new conduction disturbances and the grade of paravalvular leakage after TAVI.

Transcatheter aortic valve implantation (TAVI) in the presence of a preexisting mitral prosthesis is challenging and its influence on the morphology of mitral prosthesis and the positioning of transcatheter heart valve (THV) is unknown. We assessed the feasibility of TAVI for patients with preexisting mitral prostheses, its influence on mitral prosthesis morphology, and the positional interaction between a newly implanted THV and mitral prosthesis using serial multidetector computed tomography (MDCT). Thirty-one patients with preexisting mitral prosthesis undergoing TAVI were included. MDCT was performed before and after TAVI. Thirty patients successfully underwent TAVI without interference from preexisting mitral prosthesis. Although opening disturbance of the mechanical mitral prosthesis by the THV edge was observed in 1 patient, the patient was managed conservatively. No THV embolization occurred. THV shift during deployment occurred in 9 patients and was predicted by a larger aortic annulus area (odds ratio: 1.24 per 10 mm2, 1.03–1.49, p = 0.02), possibly because of large THVs. The mitral mean pressure gradient was slightly higher after TAVI (3.7 vs. 4.3 mmHg, p = 0.002), whereas the mitral regurgitation grade was similar. MDCT showed that the size of the mitral prosthesis housing was unchanged after TAVI. The median distance between the mitral prosthesis and THV was 2.6 mm. The postprocedural angle between the mitral prosthesis and THV was larger than the preprocedural angle between the mitral prosthesis and the left ventricular outflow tract (64° vs. 61°, p = 0.03). Thus, TAVI is feasible in the case of preexisting mitral prosthesis. Serial MDCT demonstrated favorable THV positioning and unchanged mitral prosthesis morphology after TAVI.

ObjectivesTo assess the impact of conventional transcatheter heart valve (THV) commissural alignment techniques on THV/coronary overlap and coronary access (CA) after transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV).BackgroundSpecific Evolut Pro/Pro + and Acurate Neo2 THV orientations are associated with reduced neo-commissural overlap with coronary ostia in tricuspid aortic anatomy. Whether standard orientation techniques are effective also in the setting of BAV anatomy has not been studied.MethodsThe DA VINCI (Definition of trAnscatheter aortic Valve orIeNtation in biCuspId aortic valve) pilot study is a prospective registry enrolling consecutive patients with severe BAV stenosis undergoing TAVR with last generation supra-annular tall-frame THVs implanted with a cusp overlap view-based commissural alignment. Patients underwent pre- and post-TAVR computed tomography (CT) and coronary angiography. The study endpoint was the rate of favorable THV/coronary overlap, defined as an angle > 40° between the THV commissural post and coronary ostia. Other endpoints were the rates of successful THV alignment with respect to the raphe and of selective CA after TAVR. Moreover, different virtual THV alignment models were tested to identify which one would produce the lower degree of THV/coronary overlap.ResultsThirty-four patients with type 1 BAV with right-left raphe undergoing TAVR (23 with Evolut Pro/Pro + and 11 with Acurate Neo2) were included. At pre-TAVR CT, moderate/severe cusp asymmetry was found in 50% of patients, severe coronary ostia eccentricity was observed in 47.1% for the RCA vs. 8.8% for the LCA (P < 0.007). Correct TVH orientation was achieved in 29 cases. At post-TAVR CT, optimal THV alignment/mild misalignment to the raphe was observed in 86.2%, but a moderate/severe overlap with the coronaries was seen in 13.7% for the RCA and 44.8% for the LCA (P = 0.019). After TAVR, selective RCA cannulation was possible in 82.8% vs. 75.9% for the LCA (P = 0.74), while combined selective CA of both coronaries was possible in less than two-thirds of the patients. Virtual THV alignment in the coronary ostia overlap view assuming a hypothetical circular THV expansion would produce an optimal THV/coronary overlap in almost 90% of cases.ConclusionGiven cusp asymmetry and coronary ostia eccentricity of BAV combined with potential THV asymmetrical expansion, conventional commissural alignment techniques are associated with higher rates of THV misalignment and of moderate/severe neo-commissure overlap with the coronary ostia as compared to tricuspid aortic stenosis, resulting in lower rates of selective CA after TAVR. A modified THV orientation technique based on the coronary ostia overlap view might be preferable in BAV patients.

Backgrounds Transcatheter aortic valve replacement (TAVR) improves hemodynamic disturbances in severe aortic stenosis (AS). Several translational studies have highlighted shear stress-induced inflammation, oxidative stress and primary hemostasis disorder in AS, as well as their improvement following TAVR. However, the relationship between residual shear stress and TAVR outcomes remains unclear. Purpose This study aimed to evaluate the impact of residual shear rate after the deployment of transcatheter heart valve (THV) on heart failure (HF) following TAVR. Methods A total of 939 patients with available data of shear rate after the THV deployment were included in the analysis from our prospective registry. Patients undergoing TAVR for aortic regurgitation and valve-in-valve procedures were excluded. Shear rate before and after the THV deployment were calculated using echocardiography as: 4×max aortic valve velocity/√(aortic valve area [AVA] or effective orifice area [EOA]/π). The primary endpoint was 2-year HF following TAVR, which was classified as early (≤30 days) and late events (&amp;gt;30 days). ROC curve analysis was used to derive the cut-off value of post-shear rate for the prediction of 2-year HF. Results Shear rate values significantly decreased from pre-TAVR to post-procedure (3634±865 s⁻¹ vs. 925±352 s⁻¹, p&amp;lt;0.0001). 147 patients (16%) experienced HF at 2 years following TAVR. The optimal threshold of post-shear rate for predicting 2-year HF was 822.4 s⁻¹. Patients with a post-shear rate &amp;gt;822.4 s⁻¹ (n=528, 56%) were more likely to be women, with a lower incidence of dyslipidemia, smaller aortic annulus and AVA, higher aortic gradient, and a higher proportion of balloon-expandable valve (BEV) use. These patients also had a smaller EOA and a higher rate of impaired THV performance at discharge compared to those with a lower post-shear rate (n=411, 44%). Patients with a post-shear rate &amp;gt;822.4 s⁻¹ had a higher incidence of 2-year HF (21.2% vs. 11.0%, log-rank p&amp;lt;0.0001), primarily driven by an increased incidence of late HF (20.0% vs. 10.1%, log-rank p&amp;lt;0.0001), rather than early HF (1.5% vs. 1.0%, log-rank p=0.49) (Fig. 1A and 1B). In multivariate analysis, adjusted for age, sex, CKD, atrial fibrillation, LVEF &amp;lt;40%, impaired THV performance, and HF medications, a post- TAVR shear rate &amp;gt;822.4 s⁻¹ was independently associated with late HF and 2-year HF (aHR, 2.23, 95% CI, 1.52–3.28 and aHR, 2.16, 95% CI, 1.50–3.12, respectively). In both patients receiving BEVs and those receiving self-expandable valves (SEVs), those with a post-shear rate &amp;gt;822.4 s⁻¹ had smaller THVs and a higher incidence of 2-year HF (21.0% vs. 12.5%, log-rank p=0.015 and 21.7% vs. 9.6%, log-rank p=0.0023, respectively) (Fig. 2A and 2B). Conclusions Post-TAVR residual shear rate, regardless of valve type, is a critical determinant of late HF. Potential pathophysiological mechanisms may include early structural valve deterioration due to subclinical thrombosis or inflammation.Figure 1 Figure 2

The recent approval of transcatheter aortic valve replacement (TAVR) in patients with low operative risk has paved the way for the introduction of novel and potentially improved technologies. The safety and efficacy of these novel technologies should be investigated in randomized control trials against the contemporary TAVR devices. The objective of the LANDMARK trial is to compare the balloon-expandable Myval transcatheter heart valve (THV) series with contemporary THV (SAPIEN THV and Evolut THV series) series in patients with severe symptomatic native aortic stenosis. The LANDMARK trial (ClinicalTrials.govNCT04275726, EudraCT number 2020-000,137-40) is a prospective, randomized, multinational, multicenter, open-label, and noninferiority trial of approximately 768 patients treated with TAVR via the transfemoral approach. Patients will be allocated in a 1:1 randomization to Myval THV series (n = 384) or to contemporary THV (n = 384) (either of SAPIEN THV or Evolut THV series). The primary combined safety and efficacy endpoint is a composite of all-cause mortality, all stroke (disabling and nondisabling), bleeding (life-threatening or disabling), acute kidney injury (stage 2 or 3), major vascular complications, prosthetic valve regurgitation (moderate or severe), and conduction system disturbances (requiring new permanent pacemaker implantation), according to the Valve Academic Research Consortium-2 criteria at 30-day follow-up. All patients will have follow-up to 10 years following TAVR. The LANDMARK trial is the first randomized head-to-head trial comparing Myval THV series to commercially available THVs in patients indicated for TAVR. We review prior data on head-to-head comparisons of TAVR devices and describe the rationale and design of the LANDMARK trial.