Von Willebrand Factor Activity Association With Outcomes After Transcatheter Edge-to-Edge Mitral Valve Repair.

Background: Residual mitral regurgitation (MR) is associated with worse outcomes after transcatheter edge-to-edge mitral valve repair (TEER). Shear stress induced by MR leads to altered von Willebrand factor activity (vWF:Act) and increased closure time with adenosine diphosphate (CT-ADP). Objectives: The purpose of this study was to investigate the use of CT-ADP to monitor MR during TEER and the association between the vWF, residual MR, and clinical events post-TEER. Methods: Sixty-five patients undergoing TEER were enrolled. CT-ADP was measured at baseline, after each clip deployment, 1 hour and 24 hours post-TEER. CT-ADP values were related to vWF:Act/vWF antigen (vWF:Ag) ratio at the same time points, and MR severity was assessed by echocardiography at 1 month. Combined events of all-cause mortality and heart failure hospitalizations were evaluated at 1 year. Results: At 1 month, 32 (49%) patients had residual MR > mild (of those, 14% had MR > moderate). There was no significant change in CT-ADP values during the procedure. However, CT-ADP significantly decreased 1-hour post-TEER (P < 0.001). Patients with corrected MR demonstrated an increase in vWF:Act/vWF:Ag ratio 1-hour post-TEER. Elevated baseline vWF:Act/vWF:Ag ratio and the periprocedural percentage changes of the vWF:Act/vWF:Ag ratio (1 hour post-TEER - baseline values) were associated with the combined clinical outcome. Conclusions: CT-ADP evolution in time was not quick enough to provide real-time monitoring of MR severity during TEER. However, vWF:Act/vWF:Ag ratio at baseline and its variations following the procedure were associated with clinical outcomes. Those findings will need external validation.

Durability of transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is now utilised as a less invasive alternative to surgical aortic valve replacement (SAVR) across the whole spectrum of surgical risk. Long-term durability of the bioprosthetic valves has become a key goal of TAVI as this procedure is now considered for younger and lower-risk populations. The purpose of this article is to present a state-of-the-art overview on the definition, aetiology, risk factors, mechanisms, diagnosis, clinical impact, and management of bioprosthetic valve dysfunction (BVD) and failure (BVF) following TAVI with a comparative perspective versus SAVR. Structural valve deterioration (SVD) is the main factor limiting the durability of the bioprosthetic valves used for TAVI or SAVR, but non-structural BVD, such as prosthesis-patient mismatch and paravalvular regurgitation, as well as valve thrombosis or endocarditis may also lead to BVF. The incidence of BVF related to SVD or other causes is low (<5%) at midterm (5- to 8-year) follow-up and compares favourably with that of SAVR. The long-term follow-up data of randomised trials conducted with the first generations of transcatheter heart valves also suggest similar valve durability in TAVI versus SAVR at 10 years, but these trials suffer from major survivorship bias, and the long-term durability of TAVI will need to be confirmed by the analysis of the low-risk TAVI versus SAVR trials at 10 years.

Subclinical valve leaflet thrombosis following bioprosthetic aortic valve replacement.

PURPOSE OF REVIEW: Subclinical leaflet thrombosis (SLT) is often an incidental finding characterized by a thin layer of thrombus involving one, two or three leaflets, with typical appearance on multi-detector computed tomography (MDCT) of hypo-attenuating defect at the aortic side of the leaflet, also called hypo-attenuating leaflet thickening (HALT). SLT may occur following both transcatheter aortic replacement (TAVR) or biological surgical aortic valve replacement (SAVR). The aim of this review is to present an overview of the current state of knowledge on the incidence, diagnosis, clinical impact, and management of SLT following TAVR or SAVR. RECENT FINDINGS: SLT occurs in 10-20% of patients following TAVR and is somewhat more frequent than following SAVR (5-15%). SLT may regress spontaneously without treatment in about 50% of the cases but may also progress to clinically significant valve thrombosis in some cases. Oral anticoagulation with vitamin K antagonist is reasonable if SLT is detected by echocardiography and/or MDCT during follow-up and is generally efficient to reverse SLT. SLT is associated with mild increase in the risk of stroke but has no impact on survival. SLT has been linked with accelerated structural valve deterioration and may thus impact valve durability and long-term outcomes. SUMMARY: SLT is often an incidental finding on echocardiography or MDCT that occurs in 10-20% of patients following TAVR or 5-15% following biological SAVR and is associated with a mild increase in the risk of thrombo-embolic event with no significant impact on mortality but may be associated with reduced valve durability.

Role of Antitroponin Antibodies and Macrotroponin in the Clinical Interpretation of Cardiac Troponin.

Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.

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 (RV) longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and RV longitudinal systolic function and RV-pulmonary artery (RV-PA) coupling from baseline to 30 days and 1 year after AVR. METHODS AND RESULTS: Left ventricular (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 was associated with increased risk of the composite of death, hospitalization, and stroke at 5 years [adjusted hazard ratios (HRs) for LV LS < 15%: 1.24, 95% confidence interval (CI) 1.05-1.45, P = 0.001; TAPSE < 14 mm: 1.44, 95% CI 1.21-1.73, P < 0.001; RV-PA coupling < 0.55 mm/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.

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.

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.

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.

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.

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.

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.