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.

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.

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.

Atrioventricular conduction disorders in aortic valve infective endocarditis.

BACKGROUND: Aortic valve infective endocarditis may be complicated by high-degree atrioventricular block in up to 10-20% of cases. AIM: To assess high-degree atrioventricular block occurrence, contributing factors, prognosis and evolution in patients referred for aortic infective endocarditis. METHODS: Two hundred and five patients referred for aortic valve infective endocarditis between January 2018 and March 2021 were included in this study. A comprehensive assessment of clinical, electrocardiographic, biological, microbiological and imaging data was conducted, with a follow-up carried out over 1 year. RESULTS: High-degree atrioventricular block occurred in 22 (11%) patients. In univariate analysis, high-degree atrioventricular block was associated with first-degree heart block at admission (odds ratio 3.1; P=0.015), periannular complication on echocardiography (odds ratio 6.9; P<0.001) and severe biological inflammatory syndrome, notably C-reactive protein (127 vs 90mg/L; P=0.011). In-hospital mortality (12.7%) was higher in patients with high-degree atrioventricular block (odds ratio 4.0; P=0.011) in univariate analysis. Of the 16 patients implanted with a permanent pacemaker for high-degree atrioventricular block and interrogated, only four (25%) were dependent on the pacing function at 1-year follow-up. CONCLUSIONS: High-degree atrioventricular block is associated with high inflammation markers and periannular complications, especially if first-degree heart block is identified at admission. High-degree atrioventricular block is a marker of infectious severity, and tends to raise the in-hospital mortality rate. Systematic assessment of patients admitted for infective endocarditis suspicion, considering these contributing factors, could indicate intensive care unit monitoring or even temporary pacemaker implantation in those at highest risk.

Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices.

BACKGROUND: Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta-analysis was to study immediate and long-term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). METHODS AND RESULTS: Lesion-specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (-0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. CONCLUSIONS: TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut-offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.

Comparisons of noncoronary sinus pivot implantation (NCPI) and conventional method for transcatheter aortic valve replacement with self-expanding valve in pure aortic regurgitation (PAR).

BACKGROUND: As compared to treatment of aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) using the commercially available valves to treat pure aortic regurgitation (PAR) has a lower device success rate and higher complication rates. AIMS: The study compared the acute results between TAVR using a novel noncoronary sinus pivot implantation (NCPI) method and that using the conventional method, aiming to explore a more optimized and effective operation method for TAVR in PAR. METHODS: PAR patients who underwent TAVR with self-expanding valves in our center from September 2021 to September 2023 were enrolled were divided into the NCPI (group A, N = 16) and conventional method (group B, N = 39) groups. We analyzed the pre-operative evaluation parameters and procedural and postoperative data of the two subgroups. RESULTS: The total patients' mean age was 71.2 ± 8.7 years and most were male (61.8%), with a mean Society of Thoracic Surgeons score of 3.4 ± 1.9%. The device success rate of groups A and B was 100% and 71.8%, respectively. In group B, 48.7% had major adverse cardiac events (MACE); 46.2% patients had permanent pacemaker implantation or valve in valve implantation. None had MACE in group A. The noncoronary sinus implantation depth in NCPI was -1.1 + 1.0 and 4.2 + 3.7 mm in groups A and B (p < 0.001), respectively. CONCLUSIONS: TAVR with a self-expanding valve using the NCPI method had a higher procedure success rate and dramatically low complications than that using the conventional method in PAR patients.

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.

Decellularization and characterization of camel pericardium as a new scaffold for tissue engineering and regenerative medicine.

BACKGROUND: Valvular heart diseases (VHDs) have become prevalent in populations due to aging. Application of different biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of VHD. Aortic valve replacement using tissue-engineered xenografts is a considered approach, and the pericardium of different species such as porcine and bovine has been studied over the last few years. It has been suggested that the animal origin can affect the outcomes of replacement. METHODS: So, herein, we at first decellularized and characterized the camel pericardium (dCP), then characterized dCP with H&E staining, in vitro and in vivo biocompatibility and mechanical tests and compared it with decellularized bovine pericardium (dBP), to describe the potency of dCP as a new xenograft and bio scaffold. RESULTS: The histological assays indicated less decluttering and extracellular matrix damage in dCP after decellularization compared to the dBP also dCP had higher Young Modulus (105.11), and yield stress (1.57 ± 0.45). We observed more blood vessels and also less inflammatory cells in the dCP sections after implantation. CONCLUSIONS: In conclusion, the results of this study showed that the dCP has good capabilities not only for use in VHD treatment but also for other applications in tissue engineering and regenerative medicine.

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.

Aortic Valve Calcification Density Measured by MDCT in the Assessment of Aortic Stenosis Severity.

BACKGROUND: Aortic valve calcification (AVC) indexation to the aortic annulus (AA) area measured by Doppler echocardiography (AVCdEcho) provides powerful prognostic information in patients with aortic stenosis (AS). However, the indexation by AA measured by multidetector computed tomography (AVCdCT) has never been evaluated. The aim of this study was to compare AVC, AVCdCT, and AVCdEcho with regard to hemodynamic correlations and clinical outcomes in patients with AS. METHODS: Data from 889 patients, mainly White, with calcific AS who underwent Doppler echocardiography and multidetector computed tomography within the same episode of care were retrospectively analyzed. AA was measured both by Doppler echocardiography and multidetector computed tomography. AVCdCT severity thresholds were established using receiver operating characteristic curve analyses in men and women separately. The primary end point was the occurrence of all-cause mortality. RESULTS: Correlations between gradient/velocity and AVCd were stronger (both P≤0.005) using AVCdCT (r=0.68, P<0.001 and r=0.66, P<0.001) than AVC (r=0.61, P<0.001 and r=0.60, P<0.001) or AVCdEcho (r=0.61, P<0.001 and r=0.59, P<0.001). AVCdCT thresholds for the identification of severe AS were 334 Agatston units (AU)/cm2 for women and 467 AU/cm2 for men. On a median follow-up of 6.62 (6.19-9.69) years, AVCdCT ratio was superior to AVC ratio and AVCdEcho ratio to predict all-cause mortality in multivariate analyses (hazard ratio [HR], 1.59 [95% CI, 1.26-2.00]; P<0.001 versus HR, 1.53 [95% CI, 1.11-1.65]; P=0.003 versus HR, 1.27 [95% CI, 1.11-1.46]; P<0.001; all likelihood test P≤0.004). AVCdCT ratio was superior to AVC ratio and AVCdEcho ratio to predict survival under medical treatment in multivariate analyses (HR, 1.80 [95% CI, 1.27-1.58]; P<0.001 compared with HR, 1.55 [95% CI, 1.13-2.10]; P=0.007; HR, 1.28 [95% CI, 1.03-1.57]; P=0.01; all likelihood test P<0.03). AVCdCT ratio predicts mortality in all subgroups of patients with AS. CONCLUSIONS: AVCdCT appears to be equivalent or superior to AVC and AVCdEcho to assess AS severity and predict all-cause mortality. Thus, it should be used to evaluate AS severity in patients with nonconclusive echocardiographic evaluations with or without low-flow status. AVCdCT thresholds of 300 AU/cm2 for women and 500 AU/cm2 for men seem to be appropriate to identify severe AS. Further studies are needed to validate these thresholds, especially in diverse populations.