Predictors and 5-Year Clinical Outcomes of Pacemaker After TAVR: Analysis From the PARTNER 2 SAPIEN 3 Registries.

BACKGROUND: Conduction disturbances requiring a permanent pacemaker (PPM) are a frequent complication of transcatheter aortic valve replacement (TAVR) with few reports of rates, predictors, and long-term clinical outcomes following implantation of the third-generation, balloon-expandable SAPIEN 3 (S3) transcatheter heart valve (THV). OBJECTIVES: The aim of this study was to investigate the rates, predictors, and long-term clinical outcomes of PPM implantation following TAVR with the S3 THV. METHODS: The current study included 857 patients in the PARTNER 2 S3 registries with intermediate and high surgical risk without prior PPM, and investigated predictors and 5-year clinical outcomes of new PPM implanted within 30 days of TAVR. RESULTS: Among 857 patients, 107 patients (12.5%) received a new PPM within 30 days after TAVR. By multivariable analysis, predictors of PPM included increased age, pre-existing right bundle branch block, larger THV size, greater THV oversizing, moderate or severe annulus calcification, and implantation depth >6 mm. At 5 years (median follow-up 1,682.0 days [min 2.0 days, max 2,283.0 days]), new PPM was not associated with increased rates of all-cause mortality (Adj HR: 1.20; 95% CI: 0.85-1.70; P = 0.30) or repeat hospitalization (Adj HR: 1.22; 95% CI: 0.67-2.21; P = 0.52). Patients with new PPM had a decline in left ventricular ejection fraction at 1 year that persisted at 5 years (55.1 ± 2.55 vs 60.4 ± 0.65; P = 0.02). CONCLUSIONS: PPM was required in 12.5% of patients without prior PPM who underwent TAVR with a SAPIEN 3 valve in the PARTNER 2 S3 registries and was not associated with worse clinical outcomes, including mortality, at 5 years. Modifiable factors that may reduce the PPM rate include bioprosthetic valve oversizing, prosthesis size, and implantation depth.

Hydrodynamic Assessment of Explanted Degenerated Transcatheter Aortic Valves: Novel Insights Into Noncalcific and Calcific Mechanisms.

BACKGROUND: The etiology of transcatheter aortic valve (TAV) degeneration is poorly understood, particularly noncalcific mechanisms. OBJECTIVES: The authors sought to investigate noncalcific and calcific mechanisms of TAV degeneration and evaluate their impact on leaflet function by bench testing, imaging, and histology. METHODS: TAV explants were obtained from the EXPLANT THV registry and clinical institutions. Hydrodynamic assessment was performed using a heart valve pulse duplicator system under physiological conditions. Micro-computed tomography, high-resolution photography, high speed video, and hematoxylin and eosin staining were used to evaluate the morphological appearance, leaflet kinematics, and calcium burden of TAVs. RESULTS: A total of 14 explants were evaluated: 10 self-expanding CoreValve/Evolut TAVs (Medtronic), 3 balloon-expandable SAPIEN 3 TAVs (Edwards Lifesciences), and 1 mechanically expandable Lotus TAV (Boston Scientific). The median patient age at explantation was 73.0 years (Q1-Q3: 64.5-80.0 years), with a time to explantation of 4 years 1 month (1 year 5 months to 4 years 11 months). Six TAV explants were found to have leaflet calcification (162.4 mm3; 58.8-603.0 mm3), and 8 had no calcification detectable by micro-computed tomography and histology. All samples had impaired leaflet kinematics. There was no significant difference in the hydrodynamic mean gradient between calcified (47.2 mm Hg; 26.6-74.1 mm Hg) and noncalcified (27.6 mm Hg; 15.2-36.7 mm Hg; P = 0.28) TAVs. Leaflet calcification had a weak but nonsignificant association with the hydrodynamic mean gradient (r = 0.42; P = 0.14). CONCLUSIONS: TAV function can be severely impacted by noncalcific and calcific mechanisms of tissue degeneration. Importantly, functional stenosis can occur in TAVs in the absence of obvious and significant calcification.

Moderate aortic stenosis: Navigating the uncharted.

Aortic stenosis (AS) stands as the most common valvular heart disease in developed countries and is characterized by progressive narrowing of the aortic valve orifice resulting in elevated transvalvular flow resistance, left ventricular hypertrophy, and progressive increased risk of heart failure and sudden death. This narrative review explores clinical challenges and evolving perspectives in moderate AS, where discrepancies between aortic valve area and pressure gradient measurements may pose diagnostic and therapeutic quandaries. Transthoracic echocardiography is the first-line imaging modality for AS evaluation, yet cases of discordance may require the application of ancillary noninvasive diagnostic modalities. This review underscores the importance of accurate grading of AS severity, especially in low-gradient phenotypes, emphasizing the need for vigilant follow-up. Current clinical guidelines primarily recommend aortic valve replacement for severe AS, potentially overlooking latent risks in moderate disease stages. The noninvasive multimodality imaging approach-including echocardiography, cardiac magnetic resonance, computed tomography, and nuclear techniques-provides unique insights into adaptive and maladaptive cardiac remodeling in AS and offers a promising avenue to deliver precise indications and exact timing for intervention in moderate AS phenotypes and asymptomatic patients, potentially improving long-term outcomes. Nevertheless, what we may have gleaned from a large amount of observational data is still insufficient to build a robust framework for clinical decision-making in moderate AS. Future research will prioritize randomized clinical trials designed to weigh the benefits and risks of preemptive aortic valve replacement in the management of moderate AS, as directed by specific imaging and nonimaging biomarkers.

Pathological Mechanism and Treatment of Calcified Aortic Stenosis.

Calcified aortic stenosis (AS) is one of the most common valvular heart diseases worldwide, characterized by progressive fibrocalcific remodeling and thickening of the leaflets, which ultimately leads to obstruction of blood flow. Its pathobiology is an active and complicated process, involving endothelial cell dysfunction, lipoprotein deposition and oxidation, chronic inflammation, phenotypic transformation of valve interstitial cells, neovascularization, and intravalvular hemorrhage. To date, no targeted drug has been proven to slow down or prevent disease progression. Aortic valve replacement is still the optimal treatment of AS. This article reviews the etiology, diagnosis, and management of calcified aortic stenosis and proposes novel potential therapeutic targets.

Mitral regurgitation carries greater prognostic significance than mitral stenosis in patients undergoing transcatheter aortic valve replacement.

AIMS: This study assessed the outcomes of concomitant mitral valve disease and severe aortic stenosis in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Echocardiographic data of 813 patients with severe aortic stenosis undergoing transfemoral TAVR were collected, and clinical outcomes were analyzed for individuals with mitral stenosis and mitral regurgitation. RESULTS: The final cohort includes 788 patients with severe calcific aortic stenosis. Among single parameters of mitral stenosis, a smaller baseline mitral valve area (MVA) by the continuity equation and higher postprocedural mean mitral gradients (MMG) were associated with an increased risk of death at 1 year (P-values 0.02 and <0.01, respectively), but no correlation with outcomes was demonstrated after multivariate adjustment for major prognosticators. Mitral stenosis (based on MVA + MMG) was not associated with complications or mortality. Mitral regurgitation was present in 94.6% of the population at baseline and regressed by at least one grade post-TAVR in 28% of the patients. The improvement in mitral regurgitation was associated with a greater prosthetic effective orifice area (P-value 0.03). Significant (at least moderate) residual mitral regurgitation was correlated with short-term complications and shown to be an independent predictor of 1-year mortality (P-value 0.02, odds ratio (OR) 5.37, confidence interval 1.34-21.5). CONCLUSION: Mitral regurgitation has a greater impact on TAVR patients than mitral stenosis as assessed by functional methods.

Sex-Specific Differences in Upstream Cardiac Damage in Patients With Aortic Stenosis Undergoing TAVR.

BACKGROUND: Cardiac damage caused by aortic stenosis (AS) can be categorized into stages, which are associated with a progressively increasing risk of death after transcatheter aortic valve replacement (TAVR). OBJECTIVES: The authors investigated sex-related differences in cardiac damage among patients with symptomatic AS and the prognostic value of cardiac damage classification in women and men undergoing TAVR. METHODS: In a prospective registry, pre-TAVR echocardiograms were used to categorize patients into 5 stages of cardiac damage caused by AS. Differences in the extent of cardiac damage were compared according to sex, and its implications on clinical outcomes after TAVR were explored. RESULTS: Among 2,026 patients undergoing TAVR between August 2007 and June 2022 (995 [49.1%] women and 1,031 [50.9%] men), we observed sex-specific differences in the pattern of cardiac damage (women vs men; stage 0: 2.6% vs 3.1%, stage 1: 13.4% vs 10.1%, stage 2: 37.1% vs 39.5%, stage 3: 27.5% vs 15.6%, and stage 4: 19.4% vs 31.7%). There was a stepwise increase in 5-year all-cause mortality according to stage in women (HRadjusted: 1.43; 95% CI: 1.28-1.60, for linear trend) and men (HRadjusted: 1.26; 95% CI: 1.14-1.38, for linear trend). Female sex was associated with a lower 5-year mortality in early stages (stage 0, 1, or 2) but not in advanced stages (stage 3 or 4). CONCLUSIONS: The pattern of cardiac damage secondary to AS differed by sex. In early stages of cardiac damage, women had a lower 5-year mortality than men, whereas in more advanced stages, mortality was comparable between sexes. (SwissTAVI Registry; NCT01368250).

Dimensionless index and outcome in patients with aortic valve disease.

PURPOSE: Assessment of aortic stenosis (AS) is based on aortic valve (AV) gradients and calculation of aortic valve area (AVA). These parameters are influenced by flow and dependent on geometric assumptions. The dimensionless index (DI), the ratio of the LVOT time-velocity integral to that of the AV jet, is simple to perform, and is less susceptible to error but has only been examined in small selected groups of AS patients. The objective of this study was to assess the DI and prognosis in a large cohort. METHODS: All subjects who underwent echocardiography with an assessment of the AV that included DI were included. Association between AV parameters including mean gradient, AVA, DI and AV resistance and mortality and cardiovascular hospitalizations was examined. RESULTS: A total of 9393 patients (mean age 71 ± 16 years; 53% male) were included. 731 (7.7%) patients had DI less than .25. Increasing age and a diagnosis of heart failure were significantly associated with lower DI. Subjects with low DI had significantly lower ventricular function, a higher incidence of mitral and tricuspid regurgitation, worse diastolic function and more elevated pulmonary pressures. Decreasing DI was associated with significantly decreased survival and event-free survival which remained highly significant on multivariate analysis. CONCLUSIONS: In a large population of patients with AV disease, decreased DI, was associated with increased mortality and decreased event-free survival. The easily obtained DI identifies a broad range of AS subjects with worse prognosis and should be integrated into the assessment of these complex patients.

Performance and outcomes of the SAPIEN 3 Ultra RESILIA transcatheter heart valve in the OCEAN-TAVI registry.

BACKGROUND: Data on the performance of the latest-generation SAPIEN 3 Ultra RESILIA (S3UR) valve in patients who undergo transcatheter aortic valve replacement (TAVR) are scarce. AIMS: We aimed to assess the clinical outcomes, including valve performance, of the S3UR. METHODS: Registry data of 618 consecutive patients with S3UR and of a historical pooled cohort of 8,750 patients who had a SAPIEN 3 (S3) valve and underwent TAVR were collected. The clinical outcomes and haemodynamics, including patient-prosthesis mismatch (PPM), were compared between the 2 groups and in a propensity-matched cohort. RESULTS: The incidence of in-hospital death, vascular complications, and new pacemaker implantation was similar between the S3UR and the S3 groups (allp>0.05). However, both groups showed significant differences in the degrees of paravalvular leakage (PVL) (none-trivial: 87.0% vs 78.5%, mild: 12.5% vs 20.5%, ≥moderate: 0.5% vs 1.1%; p<0.001) and the incidence of PPM (none: 94.3% vs 85.1%, moderate: 5.2% vs 12.8%, severe: 0.5% vs 2.0%; p<0.001). The prevalence of a mean pressure gradient ≥20 mmHg was significantly lower in the S3UR group (1.6% vs 6.2%; p<0.001). Better haemodynamics were observed with the smaller 20 mm and 23 mm S3UR valves. The results were consistent in a matched cohort of patients with S3UR and with S3 (n=618 patients/group). CONCLUSIONS: The S3UR has equivalent procedural complications to the S3 but with lower rates of PVL and significantly better valve performance. The better valve performance of the S3UR, particularly in smaller valve sizes, overcomes the remaining issue of balloon-expandable valves after TAVR.

Quantification of functional hemodynamics in aortic valve disease using cardiac computed tomography angiography.

BACKGROUND AND OBJECTIVE: Cardiac computed tomography angiography (CTA) is the preferred modality for preoperative planning in aortic valve stenosis. However, it cannot provide essential functional hemodynamic data, specifically the mean transvalvular pressure gradient (MPG). This study aims to introduce a computational fluid dynamics (CFD) approach for MPG quantification using cardiac CTA, enhancing its diagnostic value. METHODS: Twenty patients underwent echocardiography, cardiac CTA, and invasive catheterization for pressure measurements. Cardiac CTA employed retrospective electrocardiographic gating to capture multi-phase data throughout the cardiac cycle. We segmented the region of interest based on mid-systolic phase cardiac CTA images. Then, we computed the average flow velocity into the aorta as the inlet boundary condition, using variations in end-diastolic and end-systolic left ventricular volume. Finally, we conducted CFD simulations using a steady-state model to obtain pressure distribution within the computational domain, allowing for the derivation of MPG. RESULTS: The mean value of MPG, measured via invasive catheterization (MPGInv), echocardiography (MPGEcho), and cardiac CTA (MPGCT), were 51.3 ± 28.4 mmHg, 44.8 ± 19.5 mmHg, and 55.8 ± 25.6 mmHg, respectively. In comparison to MPGInv, MPGCT exhibited a higher correlation of 0.91, surpassing that of MPGEcho, which was 0.82. Moreover, the limits of agreement for MPGCT ranged from -27.7 to 18.7, outperforming MPGEcho, which ranged from -40.1 to 18.0. CONCLUSIONS: The proposed method based on cardiac CTA enables the evaluation of MPG for aortic valve stenosis patients. In future clinical practice, a single cardiac CTA examination can comprehensively assess both the anatomical and functional hemodynamic aspects of aortic valve disease.

The hybrid (physical-computational) cardiovascular simulator to study valvular diseases.

To better understand the impact of valvular heart disease (VHD) on the hemodynamics of the circulatory system, investigations can be carried out using a model of the cardiovascular system. In this study, a previously developed hybrid (hydro-numerical) simulator of the cardiovascular system (HCS) was adapted and used. In our HCS Björk-Shiley mechanical heart valves were used, playing the role of mitral and aortic ones. In order to simulate aortic stenosis (AS) and mitral regurgitation (MR), special mechanical devices have been developed and integrated with the HCS. The simulation results proved that the system works correctly. Namely, in the case of AS - the mean pulmonary arterial pressure was increased due to increased preload of the left ventricle and the decrease in right ventricular preload was caused by a decrease in systemic arterial pressure. The severity of AS was performed based on the transaortic pressure gradient as well as using the Gorlin and Aaslid equations. In the case of severe AS, when the mean gradient was above 40 mmHg, the aortic valve orifice area was 0.5 cm2, which is in line with ACC/AHA guidelines. For the case of MR - with increasing severity of MR, there was a decrease in the left ventricular pressure and an increase in left atrial pressure. Using mechanical heart valves to simulate VHD by the HCS can be a valuable tool for biomedical research, providing a safe and controlled environment to study and understand the pathophysiology of VHD.

On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part I: Flow configuration and vortex dynamics.

Aortic valve replacement has become an increasing concern due to the rising prevalence of aortic stenosis in an ageing population. Existing replacement options have limitations, necessitating the development of improved prosthetic aortic valves. In this study, flow characteristics during systole in a stenotic aortic valve case are compared with those downstream of two newly designed surgical bioprosthetic aortic valves (BioAVs). To do so, advanced three-dimensional fluid-structure interaction simulations are conducted and dedicated analysis methods to investigate jet flow configuration and vortex dynamics are developed. Our findings reveal that the stenotic case maintains a high jet flow eccentricity due to a fixed orifice geometry, resulting in flow separation and increased vortex stretching and tilting in the commissural low-flow regions. One BioAV design introduces non-axisymmetric leaflet motion, which reduces the maximum jet velocity and forms more vortical structures. The other BioAV design produces a fixed symmetric triangular jet shape due to non-moving leaflets and exhibits favourable vorticity attenuation, revealed by negative temporally and spatially averaged projected vortex stretching values, and significantly reduced drag. Therefore, this study highlights the benefits of custom-designed aortic valves in the context of their replacement through comprehensive and novel flow analyses. The results emphasise the importance of analysing jet flow, vortical structures, momentum balance and vorticity transport for thoroughly evaluating aortic valve performance.

On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part II: Spectral analysis and anisotropy.

Severe aortic valve stenosis can lead to heart failure and aortic valve replacement (AVR) is the primary treatment. However, increasing prevalence of aortic stenosis cases reveal limitations in current replacement options, necessitating improved prosthetic aortic valves. We investigate flow disturbances downstream of severe aortic stenosis and two bioprosthetic aortic valve (BioAV) designs using advanced energy-based analyses. Three-dimensional high-fidelity fluid-structure interaction simulations have been conducted and a dedicated and novel spectral analysis has been developed to characterise the kinetic energy (KE) carried by eddies in the wavenumber space. In addition, new field quantities, i.e. modal KE anisotropy intensity as well as normalised helicity intensity, are introduced. Spectral analysis shows kinetic energy (KE) decay variations, with the stenotic case aligning with Kolmogorov's theory, while BioAV cases differing. We explore the impact of flow helicity on KE transfer and decay in BioAVs. Probability distributions of modal KE anisotropy unveil flow asymmetries in the stenotic and one BioAV cases. Moreover, an inverse correlation between temporally averaged modal KE anisotropy and normalised instantaneous helicity intensity is noted, with the coefficient of determination varying among the valve configurations. Leaflet dynamics analysis highlights a stronger correlation between flow and biomechanical KE anisotropy in one BioAV due to higher leaflet displacement magnitude. These findings emphasise the role of valve architecture in aortic turbulence as well as its importance for BioAV performance and energy-based design enhancement.

The impact of the Naples Prognostic Score on the short- and long-term prognosis of patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Preoperative systemic inflammation and nutritional status have been shown to affect prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). In this study, we investigated the effect of the Naples Prognostic Score (NPS), which consists of four different parameters including these two components on short- and long-term prognosis in patients undergoing TAVI. METHODS: In 343 patients (mean age 78.1 ±â€Š8.4 years, 51.3% female) who underwent TAVI, the NPS score was calculated from the blood tests obtained before the procedure and the study population was divided into three according to the NPS value: those with 0 and 1 were divided into Group-1, those with 2 into Group-2, and those with 3 and 4 into Group-3. The relationship between NPS group and in-hospital adverse events and long-term survival was evaluated. RESULTS: Systolic pulmonary artery pressure, STS score, presence of chronic lung disease and being in NPS Group-3 [adjusted odds ratio (adjOR): 3.93, 95% confidence interval (CI) (1.02-15.17), P  = 0.047] were found to be independent predictors of in-hospital mortality. According to the multivariate Cox-regression model, both Group-2 NPS [adjusted hazard ratio (adjHR): 4.81, 95% CI (1.09-21.14), P  = 0.037] and Group-3 NPS [adjHR: 10.1, 95% CI (2.31-43.36), P  = 0.002] was an independent predictor of 2-year all-cause mortality after TAVI. There was no significant difference in perioperative adverse events between the groups except for postprocedural acute kidney injury. According to receiver-operating characteristic analysis, the optimal predictive value of NPS for in-hospital and long-term mortality was 2.5. CONCLUSION: In patients who will be candidates for TAVI, NPS is a simple and effective tool for determining both short- and long-term prognosis.

Myocardial Blood Flow Reserve, Microvascular Coronary Health, and Myocardial Remodeling in Patients With Aortic Stenosis.

BACKGROUND: Coronary microvascular function and hemodynamics may play a role in coronary circulation and myocardial remodeling in patients with aortic stenosis (AS). We aimed to evaluate the relationship between myocardial blood flow and myocardial function in patients with AS, no AS, and aortic valve sclerosis. METHODS AND RESULTS: We included consecutive patients who had resting transthoracic echocardiography and clinically indicated positron emission tomography myocardial perfusion imaging to capture their left ventricular ejection fraction, global longitudinal strain (GLS), and myocardial flow reserve (MFR). The primary outcome was major adverse cardiovascular event (all-cause mortality, myocardial infarction, or late revascularization). There were 2778 patients (208 with aortic sclerosis, 39 with prosthetic aortic valve, 2406 with no AS, and 54, 49, and 22 with mild, moderate, and severe AS, respectively). Increasing AS severity was associated with impaired MFR (P<0.001) and GLS (P<0.001), even when perfusion was normal. Statistically significant associations were noted between MFR and GLS, MFR and left ventricular ejection fraction, and MFR and left ventricular ejection fraction reserve. After a median follow-up of 349 (interquartile range, 116-662) days, 4 (7.4%), 5 (10.2%), and 6 (27.3%) patients experienced a major adverse cardiovascular event in the mild, moderate, and severe AS groups, respectively. In a matched-control analysis, patients with mild-to-moderate AS had higher rates of impaired MFR (52.9% versus 39.9%; P=0.048) and major adverse cardiovascular event (11.8% versus 3.0%; P=0.002). CONCLUSIONS: Despite lack of ischemia, as severity of AS increased, MFR decreased and GLS worsened, reflecting worse coronary microvascular health and myocardial remodeling. Positron emission tomography-derived MFR showed a significant independent correlation with left ventricular ejection fraction and GLS. Patients with prosthetic aortic valve showed a high prevalence of impaired MFR.