Left and Right Ventricular Longitudinal Systolic Function Following Aortic Valve Replacement in the PARTNER 2 Trial And Registry.

AIMS: Evaluation of left and right ventricular longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and right ventricular longitudinal systolic function and RV-pulmonary artery (RV-PA) coupling from baseline to 30-days and 1-year after aortic valve replacement (AVR). METHODS AND RESULTS: LV longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV-PA coupling were evaluated in patients from the PARTNER-2A surgical AVR (SAVR) arm (n=985) and from the PARTNER-2 SAPIEN-3 registry (n=719). TAPSE and RV-PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV-PA coupling at baseline were associated with increased risk of the composite of death, hospitalization, and stroke at 5-years (Adjusted-HRs for LV LS<15%: 1.24 95%CI 1.05-1.45, p=0.001; TAPSE<14mm: 1.44 95%CI 1.21-1.73, p<0.001; RV/PA coupling<0.55mm/mmHg: 1.32 95% CI 1.07-1.63, p=0.011). Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5-years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95%CI 1.08-1.68, p=0.009) but not with TAVR (HR: 1.12, 95%CI 0.88-1.42). Lower RV-PA coupling at 30-days showed the strongest association with cardiac mortality. CONCLUSION: SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV-PA coupling. Lower TAPSE and RV-PA coupling at 30-days were associated with inferior clinical outcomes at 5-years. In patients with LVEF<50%, TAVR was associated with superior 5-year outcomes.

Leaflet Mechanical Stress in Different Designs and Generations of Transcatheter Aortic Valves: An in Vitro Study.

Background: It is unknown whether bioprostheses used for transcatheter aortic valve implantation will have similar long-term durability as those used for surgical aortic valve replacement. Repetitive mechanical stress applied to the valve leaflets, particularly during diastole, is the main determinant of structural valve deterioration. Leaflet mechanical stress cannot be measured in vivo. The objective of this in vitro/in silico study was thus to compare the magnitude and regional distribution of leaflet mechanical stress in old vs new generations of self-expanding (SE) vs balloon expandable (BE) transcatheter heart valves (THVs). Methods: A double activation simulator was used for in vitro testing of two generations of SE THV (Medtronic CoreValve 26 mm and EVOLUT PRO 26 mm) and two generations of BE THV (Edwards SAPIEN 23 mm vs SAPIEN-3 23 mm). These THVs were implanted within a 21-mm aortic annulus. A noncontact system based on stereophotogammetry and digital image correlation with high spatial and temporal resolution (2000 img/sec) was used to visualize the valve leaflet motion and perform the three-dimensional analysis. A finite element model of the valve was developed, and the leaflet deformation obtained from the digital image correlation analysis was applied to the finite element model to calculate local leaflet mechanical stress during diastole. Results: The maximum von Mises leaflet stress was higher in early vs new THV generation (p < 0.05) and in BE vs SE THV (p < 0.05): early generation BE: 2.48 vs SE: 1.40 MPa; new generation BE: 1.68 vs SE: 1.07 MPa. For both types of THV, the highest values of leaflet stress were primarily observed in the upper leaflet edge near the commissures and to a lesser extent in the mid-portion of the leaflet body, which is the area where structural leaflet deterioration most often occurs in vivo. Conclusions: The results of this in vitro/in silico study suggest that: i) Newer generations of THVs have ∼30% lower leaflet mechanical stress than the early generations; ii) For a given generation, SE THVs have lower leaflet mechanical stress than BE THVs. Further studies are needed to determine if these differences between new vs early THV generations and between SE vs BE THVs will translate into significant differences in long-term valve durability in vivo.

Association between remnant cholesterol and progression of bioprosthetic valve degeneration.

AIMS: Remnant cholesterol (RC) seems associated with native aortic stenosis. Bioprosthetic valve degeneration may share similar lipid-mediated pathways with aortic stenosis. We aimed to investigate the association of RC with the progression of bioprosthetic aortic valve degeneration and ensuing clinical outcomes. METHODS AND RESULTS: We enrolled 203 patients with a median of 7.0 years (interquartile range: 5.1-9.2) after surgical aortic valve replacement. RC concentration was dichotomized by the top RC tertile (23.7 mg/dL). At 3-year follow-up, 121 patients underwent follow-up visit for the assessment of annualized change in aortic valve calcium density (AVCd). RC levels showed a curvilinear relationship with an annualized progression rate of AVCd, with increased progression rates when RC >23.7 mg/dL (P = 0.008). There were 99 deaths and 46 aortic valve re-interventions in 133 patients during a median clinical follow-up of 8.8 (8.7-9.6) years. RC >23.7 mg/dL was independently associated with mortality or re-intervention (hazard ratio: 1.98; 95% confidence interval: 1.31-2.99; P = 0.001). CONCLUSION: Elevated RC is independently associated with faster progression of bioprosthetic valve degeneration and increased risk of all-cause mortality or aortic valve re-intervention.

Prognostic utility of N-terminal pro B-type natriuretic peptide ratio in mixed aortic valve disease.

OBJECTIVE: We aimed to assess the incremental prognostic value of N-terminal-pro-B-type natriuretic peptide (Nt-proBNP) for risk stratification in mixed aortic valve disease (MAVD) patients. METHODS: We included 556 (73±12 years, 37% women) consecutive patients with at least a moderate aortic stenosis (AS) or aortic regurgitation (AR) lesion with a concomitant AS or AR of any severity in whom Nt-proBNP was measured and expressed as its ratio (measured Nt-proBNP divided by the upper limit of normal Nt-proBNP for age and sex). The primary endpoint was all-cause mortality. RESULTS: Baseline median Nt-proBNP ratio was 3.8 (IQR: 1.5-11.3), and the median follow-up was 5.6 years (4.8-6.1). Early aortic valve replacement (AVR) was performed within 3 months in 423 (76%) patients, while 133 (24%) remained initially under medical treatment. In comprehensive multivariable analyses, Nt-proBNP ratio was significantly associated with excess mortality (continuous variable: HR (95% CI): 1.24 (1.04 to 1.47), p=0.02; Nt-proBNP ratio ≥3: 2.41 (1.33 to 4.39), p=0.004). The independent prognostic value was also observed in patients with severe or non-severe AS/AR, and those treated by early-AVR (all p<0.04). Nt-proBNP ratio as continuous and dichotomic (≥3) variables showed incremental prognostic value (all net reclassification index >0.42, all p≤0.008). After early-AVR, Nt-proBNP ratio ≥3 was associated with higher 30-day mortality (9 (4%) vs 1 (0.5%), p=0.02). CONCLUSIONS: In this series of MAVD patients, Nt-proBNP ratio was a powerful predictor of early and long-term mortality, even in patients with both non-severe AS/AR. Moreover, early-AVR may be an option for patients with Nt-proBNP ratio ≥3. Further randomised studies are needed to validate this last point.

Long-term echocardiographic data, mechanisms of failure, and reintervention outcomes of the Epic valve in mitral position-a large observational cohort.

OBJECTIVES: Long-term echocardiographic reports on mitral valve (MV) porcine xenograft bioprosthesis (Epic) are lacking, and postreintervention outcomes of failed Epic are unknown. We aimed to assess the mechanisms and independent predictors of Epic failures and to compare short- and mid-term outcomes according to reintervention type. METHODS: We included consecutive patients (n = 1397; mean age: 72 ± 8 years; 46% female; mean follow-up: 4.8 years) who received the Epic during mitral valve replacement (MVR) at our institution. Clinical, echocardiographic, reintervention, and outcomes data were retrieved from our prospective institution's database or government statistics. RESULTS: Gradients and effective orifice area of the Epic were stable over 5-years follow-up. A total of 70 (5%) patients had a MV reintervention at median follow-up of 3.0 (0.7-5.4) years due to prosthesis failure, by redo-MVR (n = 38; 54%), valve-in-valve (n = 19; 27%), paravalvular leak (PVL) closure (n = 12; 17%), or thrombectomy (n = 1). Mechanisms of failure were 27 (1.9%) structural valve deterioration (SVD; all leaflet tear); 16 (1.1%) non-SVD (15 PVL, 1 pannus); 24 (1.7%) endocarditis; and 4 (0.3%) thrombosis. Freedom from all-cause and SVD-related MV reintervention at 10 years are 88% and 92%, respectively. Independent predictors of reintervention were age, baseline atrial fibrillation, initial MV etiology, and moderate or greater PVL at discharge (all P ≤ .05). Comparison of redo-MVR and valve-in-valve revealed no significant difference in early outcomes or mid-term mortality (all P ≥ .16). CONCLUSIONS: The Epic Mitral valve has stable hemodynamics through 5 years and is associated with low incidence of SVD and reintervention, mostly due to endocarditis and leaflet tear without calcification. Reintervention type had no influence on early outcomes and mid-term mortality.

Radioprotection for the imaging specialist during structural heart interventions: Not an option!

Structural heart interventions are steadily increasing, and the majority requires echocardiographic guidance. As a result, imaging specialists are exposed to the harmful effects of scattered ionizing radiation. This X-ray exposure must be quantified, its potential consequences should be monitored by occupational medicine and the "as low as reasonably achievable" principles of radioprotection should be optimized (including increasing the distance, decreasing the duration, using shielding radiation and providing safety training for the imaging specialist). The spatial organization of and shielding provision in the procedural rooms should be designed to optimize radioprotection for all team members.

Percutaneous Transcatheter Edge-to-Edge Mitral Valve Repair With MitraClip System in the Era of G4.

The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.

Integrating Echocardiography Parameters With Explainable Artificial Intelligence for Data-Driven Clustering of Primary Mitral Regurgitation Phenotypes.

BACKGROUND: Primary mitral regurgitation (MR) is a heterogeneous clinical disease requiring integration of echocardiographic parameters using guideline-driven recommendations to identify severe disease. OBJECTIVES: The purpose of this preliminary study was to explore novel data-driven approaches to delineate phenotypes of MR severity that benefit from surgery. METHODS: The authors used unsupervised and supervised machine learning and explainable artificial intelligence (AI) to integrate 24 echocardiographic parameters in 400 primary MR subjects from France (n = 243; development cohort) and Canada (n = 157; validation cohort) followed up during a median time of 3.2 years (IQR: 1.3-5.3 years) and 6.8 (IQR: 4.0-8.5 years), respectively. The authors compared the phenogroups' incremental prognostic value over conventional MR profiles and for the primary endpoint of all-cause mortality incorporating time-to-mitral valve repair/replacement surgery as a covariate for survival analysis (time-dependent exposure). RESULTS: High-severity (HS) phenogroups from the French cohort (HS: n = 117; low-severity [LS]: n = 126) and the Canadian cohort (HS: n = 87; LS: n = 70) showed improved event-free survival in surgical HS subjects over nonsurgical subjects (P = 0.047 and P = 0.020, respectively). A similar benefit of surgery was not seen in the LS phenogroup in both cohorts (P = 0.70 and P = 0.50, respectively). Phenogrouping showed incremental prognostic value in conventionally severe or moderate-severe MR subjects (Harrell C statistic improvement; P = 0.480; and categorical net reclassification improvement; P = 0.002). Explainable AI specified how each echocardiographic parameter contributed to phenogroup distribution. CONCLUSIONS: Novel data-driven phenogrouping and explainable AI aided in improved integration of echocardiographic data to identify patients with primary MR and improved event-free survival after mitral valve repair/replacement surgery.

Sex-specific correlates of valvular and arterial calcification burden in patients with moderate aortic stenosis.

INTRODUCTION: There are significant sex differences in the prevalence and severity of cardiac calcifying processes. Women harbour more severe mitral annular calcification (MAC), while men exhibit worse aortic valve (AVC) and coronary artery (CAC) calcification. To better understand these differences, we investigated the correlates of cardiac calcification according to sex. METHODS: We conducted a cross-sectional study of 406 patients with ≥mild aortic stenosis (AS) defined by an aortic valve area ≤1.5 cm2, a peak aortic jet velocity >2.0 m/s, or a mean transvalvular gradient >15 mm Hg. Doppler-echocardiography and non-contrast multidetector CT were performed concomitantly to assess AS and cardiac calcifications. RESULTS: Mean age was 71±11 years and 33% were women. The AS haemodynamics were not significantly different between sexes (all p>0.50), with a mean indexed aortic valve area of 0.59±0.21 cm2/m2, peak aortic jet velocity of 2.78 (2.37-3.68) m/s, and mean gradient of 17.9 (12.8-31.3) mm Hg for the whole cohort. Compared with men, women harboured lower AVC (480 (222-1191) vs 1003 (484-2329) Agatston unit, AU; p<0.0001) and CAC (366 (50-914) vs 618 (167-1357) AU; p=0.007), but more severe MAC (60 (1-887) vs 48 (0-351) AU; p=0.08) and ascending aorta calcification (227 (43-863) vs 142 (7-493) AU; p=0.03). After comprehensive adjustment, sex remained an independent predictor of each cardiac calcification subtype (all p<0.02) except for the ascending aorta (p=0.32). In multivariable analysis, certain variables, like age or bicuspid aortic valve, were associated with the calcification scores in both sexes. Sex-specific predictors of calcification burden were absence of angiotensin receptor blockers (ß=-0.26; p=0.007) and renal impairment (ß=0.26; p=0.003) for AVC, and bisphosphonates (ß=0.20; p=0.05) for CAC in women; coronary artery disease (ß=0.25; p=0.001) for AVC, and angiotensin receptor blockers (ß=0.19; p=0.02) and calcium/vitamin D (ß=0.15; p=0.02) for MAC in men. CONCLUSION: In AS, factors associated with cardiac valvular and arterial calcification differ between sexes, suggesting an important contributory role of sex in the pathophysiology of these calcifying processes.

Standardized Definitions for Bioprosthetic Valve Dysfunction Following Aortic or Mitral Valve Replacement: JACC State-of-the-Art Review.

Bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF) may be caused by structural or nonstructural valve dysfunction. Both surgical and transcatheter bioprosthetic valves have limited durability because of structural valve deterioration. The main objective of this summary of experts participating in a virtual workshop was to propose standardized definitions for nonstructural and structural BVD and BVF following aortic or mitral biological valve replacement with the goal of facilitating research reporting and implementation of these terms in clinical practice. Definitions of structural BVF, based on valve reintervention or death, underestimate the true incidence of BVF. However, definitions solely based on the presence of high transprosthetic gradient at a given echocardiogram during follow-up overestimate the incidence of structural BVD and BVF. Definitions of aortic or mitral structural BVD must therefore include the confirmation by imaging of permanent structural changes to the leaflets alongside evidence of deterioration in valve hemodynamic function at echocardiography follow-up.

Experience of Combined Procedure during Percutaneous LAA Closure.

INTRODUCTION: Percutaneous left atrial appendage closure (LAAC) is an alternative to oral anticoagulants (OAC) in patients with non-valvular atrial fibrillation (AF) and contraindication to long-term OAC. Combined strategy with percutaneous LAAC at the same time of other cardiac structural or electrophysiological procedures has emerged as an alternative to a staged strategy. AIM: To describe our experience with combined LAAC procedures using Watchman™ devices. METHODS: All patients with combined LAAC procedures using Watchman™ (WN) devices performed from 2016 to 2021 were included. The primary safety endpoint was a composite of periprocedural complications and adverse events during the follow-up. The primary efficacy endpoint included strokes, systemic embolisms, major bleeding and cardiovascular death. RESULTS: From 2016, among 160 patients who underwent LAAC using WN devices, 19 underwent a combined strategy: 7 transcatheter edge-to-edge mitral valve repair (TEMVR) (37%), 6 typical atrial flutter ablation (31%), 2 leadless pacemaker (LP) implantation (10%) and 4 AF ablation (22%). The WN device was successfully implanted in 98% and 100% of cases for single and combined LAAC procedures, respectively (p = 0.63). Median follow-up was 13 months (IQR 25/75 3/24). Device-related complications occurred in 6 out of 141 patients (4%) who underwent single LAAC and in no (0/19) patient in the combined LAAC procedure (p = ns). The procedural-related complications did not differ significantly between groups (5% vs. 10%, respectively, in the single and combined group, p = 0.1). CONCLUSION: Combined procedure using the Watchman™ devices and one other structural or electrophysiological procedure appears safe and effective. Larger series are needed to confirm these results.

5-Year Follow-Up From the PARTNER 2 Aortic Valve-in-Valve Registry for Degenerated Aortic Surgical Bioprostheses.

OBJECTIVES: The aim of this study was to report the outcomes of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) at 5 years. BACKGROUND: TAVR for degenerated surgical bioprostheses in patients at high risk for reoperative surgery is an important treatment option that may delay or obviate the need for surgical intervention; however, long-term outcomes of this procedure are unknown. METHODS: The PARTNER (Placement of Aortic Transcatheter Valves) 2 ViV and continued access registries prospectively enrolled patients with failed surgical bioprostheses at high risk for reoperation. Five-year clinical and echocardiographic follow-up data were obtained in 95.9% of patients. RESULTS: In 365 (96 registry and 269 continued access) patients, the mean age was 78.9 ± 10.2 years, the mean Society of Thoracic Surgeons predicted risk of surgical mortality score was 9.1 ± 4.7%, and New York Heart Association functional class was III or IV in 90.4%. At 5 years, the Kaplan-Meier rates of all-cause mortality and any stroke were 50.6% and 10.5%, respectively. Using Valve Academic Research Consortium 3 definitions, the incidence of structural valve deterioration, related hemodynamic valve deterioration, or bioprosthetic valve failure at 5 years was 6.6%. Aortic valve re-replacement was performed in 6.3% (n = 14), the majority of which was due to stenosis (n = 6) and combined aortic insufficiency/paravalvular regurgitation (n = 3). The mean gradient, Doppler velocity index, paravalvular regurgitation, and quality of life measured by Kansas City Cardiomyopathy Questionnaire scores in survivors remained stable from 30 days postprocedure through 5 years. CONCLUSIONS: At the 5-year follow-up, TAVR for bioprosthetic aortic valve failure in high surgical risk patients was associated with sustained improvement in clinical and echocardiographic outcomes.