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Pathological tissues release a variety of factors, including extracellular vesicles (EVs) shed by activated or apoptotic cells. EVs trapped within the native pathological valves may act as key mediators of valve thrombosis. Human aortic stenosis EVs promote activation of valvular endothelial cells, leading to endothelial dysfunction, and proadhesive and procoagulant responses.
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Aortic Stenosis (AS) is a common condition with an estimated pooled prevalence of all AS in the elderly population at around 12.4%, with that of severe AS estimated to be around 3.4%. In the past, surgical aortic valve replacement was the primary treatment option for severe AS for decades. However, with the compelling evidence on the safety and efficacy of transcatheter aortic valve replacement (TAVR), it has become the gold standard treatment option for many patients with symptomatic severe AS. Transfemoral access has been the preferred method for transcatheter heart valve delivery. However, the prevalent use of TAVR on a diverse patient profile with different risk factors, such as peripheral artery disease, precluded the possibility of a transfemoral approach despite the improvement of valves and delivery systems technology. Therefore, alternative TAVR approaches have gained increasing utility in cases where transfemoral access is unfavorable. We review the journey, evolution, and techniques for different approaches of percutaneous TAVR, including transfemoral, transcarotid, transsubclavian/transaxillary, and transcaval approaches, in addition to the traditional "surgical" transaortic and transapical accesses. Consolidating these data highlights each approach's practicality and limitations, providing additional grounding for case-by-case utilization and future clinical research.
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Purpose: The impact of aortic stenosis (AS) severity on multidirectional myocardial function in patients with bicuspid aortic valve (BAV) remains unclear, despite the recognized presence of early left ventricular longitudinal myocardial dysfunction in BAV patients with normal valve function. The aim of the study was to evaluate the multidirectional myocardial functions of BAV patients. Methods: A total of 86 BAV patients (age 46.71 ± 13.62 years, 69.4% men) with normally functioning (BAV-nf), mild AS, moderate AS, and severe AS with preserved left ventricular ejection fraction (LVEF ≥ 52%) were included. 30 healthy volunteers were recruited as the control group. Multidirectional strain and volume analysis were performed by three-dimensional speckle tracking echocardiography(3D-STE). Results: Global longitudinal strain (GLS), and global radial strain (GRS) were reduced in BAV-nf patients compared with the controls. With each categorical of AS severity from BAV-nf to severe AS, there was an associated progressive impairment of GLS and GRS (all P < 0.001). Global circumferential strain (GCS) did not show a significant decrease from BAV-nf to mild AS but began to decrease from moderate AS. Multiple linear regressions indicated that indexed aortic valve area (AVA/BSA), as a measure of AS severity, was an independent determinant of GLS, GCS and GRS. Conclusions: Left ventricular longitudinal myocardial reduction is observed even in patients with well-functioning bicuspid aortic valves. With each categorical increase in the grade of AS severity from normally functioning to severe aortic stenosis, there was an associated progressive impairment of longitudinal myocardial function. Furthermore, circumferential myocardial function was starting damaged from moderate AS. AVA/BSA was independently associated with multidirectional myocardial function injuries.
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Familial hypercholesterolemia (FH) is a prevalent and underrecognized disorder. A young girl with previously undiagnosed homozygous FH presented with acute coronary syndrome. Severe coronary ostial stenosis and severe supravalvular aortic stenosis from atheromatous plaque was discovered. This case highlights the importance of screening and timely diagnosis of FH.
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Concomitant aortic stenosis and coronary artery disease in the elderly population is frequent and the proper therapeutic approach is a matter of debate. We present 2 challenging cases of patients affected by severe aortic stenosis and chronic total occlusion of the left main, demonstrating the safety and feasibility of transcatheter aortic valve replacement, performed both with balloon-expandable and self-expanding valves.
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A 32-year-old pregnant woman from a remote area presented with chest pain and was diagnosed with critical aortic stenosis. Her care was managed by a multidisciplinary team with virtual consultations arranged until her admission. She successfully delivered with all necessary backup facilities in place to manage potential complications.
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OBJECTIVES: We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). METHODS: Data from 2 prospective registries, the INSPIRIS RESILIA Durability Registry (INDURE) and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. The PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. RESULTS: Females had a lower body mass index (median 27.1 vs 28.0 kg/m2; P = 0.008), fewer bicuspid valves (52% vs 59%; P = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; P < 0.001) and Society of Thoracic Surgeons score (mean 1.6 vs 0.9%; P < 0.001), were more often in New York Heart Association functional class III/IV (47% vs 30%; P < 0.001) and angina Canadian Cardiovascular Society III/IV (8.2% vs 4.4%; P < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; P = 0.028) compared to males. These differences vanished after PSM, except for the EuroSCORE II and Society of Thoracic Surgeons scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, P < 0.001). There were no differences in the length of hospital stay (median 8 days) or intensive care unit stay (median 24 vs 25 hours) between the 2 sexes. At 2 years, post-SAVR outcomes were comparable between males and females, even after PSM. CONCLUSIONS: Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females.
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AIMS: To characterize left atrial (LA) and left ventricular (LV) function and atrioventricular (AV) coupling in patients with moderate mixed aortic valve disease (MMAVD) against those with isolated moderate or severe aortic valve disease and controls. METHODS & RESULTS: Retrospective LA and LV peak longitudinal strain (LS) analysis were performed on 260 patients (46 MMAVD, 81 moderate aortic stenosis (AS), 50 severe AS, 48 moderate aortic regurgitation (AR), and 35 severe AR) and 66 controls. Peak LV and LA LS and AV coupling, assessed by combined peak LA and LV strain, was compared between the groups. ANOVA and 2-sided t-tests were used and a p-value of <0.01 was considered significant.LV strain was significantly lower in those with MMAVD compared to controls and those with moderate or severe isolated AR but comparable to those with moderate or severe AS (-17.1±1.1% MMAVD vs. -17.7±1.5% moderate AS p=0.02; vs. -17.0%±1.5% severe AS, p=0.74). AV coupling was significantly lower in those with MMAVD compared to controls and those with moderate AS or AR but comparable to those with severe AS or AR (47.1±6.8% MMAVD vs. 45.1±5.6% severe AS, p=0.13; vs. 50.4±9% severe AR, p=0.07). CONCLUSIONS: Impairments in AV coupling are comparable for patients with MMAVD and those with severe isolated AS or AR. Impairments in LV GLS in MMAVD mirror those found in severe AS. These findings suggest that haemodynamic consequences and adverse remodelling are similar for patients with MMAVD and isolated severe disease.
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BACKGROUND: The development of heart failure is a turning point in the natural course of aortic stenosis (AS). Pulmonary oedema and elevated left ventricular pressure (LVP) are cardinal features of heart failure. Evaluating pulmonary oedema by lung ultrasound involves taking the upper hand with a bedside noninvasive tool that may reflect LVP. AIM: We sought to assess the correlation between sonographic pulmonary congestion, invasive LV pre-A pressure, and echocardiographic LV end-diastolic pressure (LVEDP) in symptomatic AS patients receiving transcatheter aortic valve replacement. METHODS: Forty-eight consecutive patients with severe AS and planned transcatheter aortic valve implantation (TAVI) were enrolled. LVEDP was estimated to be normal or elevated using the ASE/EACVI algorithm and transmitral Doppler indices, the E/A ratio, the E/e', and the left atrial volume index. Invasive LV pre-A pressure was used as a reference, with > 12 mm Hg defined as elevated. RESULTS: Forty-eight patients (25 women (52%), mean age 75 years, standard deviation (SD) ± 7.7 years) were enrolled in the study. We detected severe B-lines (≥ 30) in 13 (27%) patients and moderate B-lines (15-30) in 33 (68.6%) patients. The number of B-lines increased significantly with the severity of New York Heart Association (NYHA) functional classes (Fig. 1). The B-line count was 14 ± 13 in NYHA class I patients, 20 ± 20 in class II patients, and 44 ± 35 in class III patients (p < 0.05, rho = 0.384). The number of B-lines was correlated with the E/E' ratio (R = 0.664, p < 0.0001) and the proBNP level (R = 0. 882, p < 0.008). We found no significant correlation with the LVEDP or LVEF. The LVEDP correlated well with the E/E' ratio (R = 0.491, p < 0.001) but not at all with E/A, DT, or LAVI. All patients had an elevated LVEDP > 12, with a mean pressure of 26 mmHg, a minimum of 13 mmHg, and a maximum of 45 mmHg, with an SD of 7.85. CONCLUSION: Assessing lung ultrasonic B-lines is a straightforward and practical approach to identifying pulmonary oedema in AS patients. The number of B-lines correlated with the E/E' ratio and the functional status of patients but did not correlate with invasive LVEDP or LVEF. All patients had elevated LVEDP that correlated with E/E'.
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BACKGROUND: Older adults with severe aortic stenosis (AS) may receive care in a nursing home (NH) prior to undergoing transcatheter aortic valve replacement (TAVR). NH level of care can be used to stabilize medical conditions, to provide rehabilitation services, or for long-term care services. Our primary objective is to determine whether NH utilization pre-TAVR can be used to stratify patients at risk for higher mortality and poor disposition outcomes at 30 and 365 days post-TAVR. METHODS: We conducted a retrospective cohort study among Medicare beneficiaries who spent ≥1 day in an NH 6 months before TAVR (2011-2019). The intensity of NH utilization was categorized as low users (1-30 days), medium users (31-89 days), long-stay NH residents (≥ 100 days, with no more than a 10-day gap in care), and high post-acute rehabilitation patients (≥90 days, with more than a 10-day gap in care). The probabilities of death and disposition were estimated using multinomial logistic regression, adjusting for age, sex, and race. RESULTS: Among 15,581 patients, 9908 (63.6%) were low users, 4312 (27.7%) were medium users, 663 (4.3%) were high post-acute care rehab users, and 698 (4.4%) were long-stay NH residents before TAVR. High post-acute care rehabilitation patients were more likely to have dementia, weight loss, falls, and extensive dependence of activities of daily living (ADLs) as compared with low NH users. Mortality was the greatest in high post-acute care rehab users: 5.5% at 30 days, and 36.4% at 365 days. In contrast, low NH users had similar mortality rates compared with long-stay NH residents: 4.8% versus 4.8% at 30 days, and 24.9% versus 27.0% at 365 days. CONCLUSION: Frequent bouts of post-acute rehabilitation before TAVR were associated with adverse outcomes, yet this metric may be helpful to determine which patients with severe AS could benefit from palliative and geriatric services.
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PURPOSE: Congenital aortic stenosis is a common pathology in the childhood age group and its clinical spectrum varies between asymptomatic and severe heart failure. In our study, we planned to evaluate the long-term results of patients who underwent balloon aortic valvuloplasty (BAV) due to critical aortic valve stenosis in our clinic. MATERIALS AND METHODS: Patients aged 0-18 years who underwent aortic balloon valvuloplasty due to aortic stenosis in our clinic between January 2002 and January 2022 were retrospectively evaluated. RESULTS: Among the 48 patients who underwent balloon valvuloplasty due to aortic stenosis, 13 (27%) were female, and 35 (73%) were male. The median age at the time of the procedure was 27.5 months (IQR: 4-96), the median weight was 9.9 kg (IQR: 5.40-29.50), and the median height was 79 cm (IQR: 54-133). The median follow-up duration was 93.5 months (IQR: 38-132). Angiographic assessments in all patients revealed a median left ventricular pressure of 160 mmHg (IQR: 140-200) and a median pressure gradient between the left ventricle and the aorta of 60 mmHg (IQR: 42-80). The median balloon diameter used was 10 mm (IQR: 8-12). Post-procedural measurements showed a median mean gradient of 30 mmHg (IQR: 20-35) between the left ventricle and the aorta. The procedure was successful in 45 (93.5%) patients. During follow-up, 11 patients required surgical intervention. Ross procedure was performed in five patients, homograft in five patients, and mechanical valve implantation in one patient. Risk factors for the need for surgical intervention were evaluated in detail. During the follow-up, the risk factor for intervention was determined to be aortic insufficiency. CONCLUSION: Aortic valve balloon valvuloplasty is a safe and successful treatment method for critical aortic stenosis. It should be the first choice of treatment option in suitable patients.
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BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) can manifest as rhythm disorders, heart failure, but also valvular degeneration. Despite aortic stenosis (AS) being prevalent among the elderly, data on ATTR-CM prevalence and outcome in patients with AS undergoing transaortic valve implantation (TAVI) remain scarce. AIM: To determine ATTR-CM prevalence and evaluate 1-year survival in patients undergoing TAVI. METHODS: Between December 2020 and September 2021, 100 consecutive patients underwent TAVI and were screened prospectively for ATTR-CM using bone scintigraphy (BS). Monoclonal gammopathy was ruled out in case of cardiac uptake on BS. All patients were followed prospectively for 1year after TAVI. RESULTS: The proportion of patients aged≥75years or with a EuroSCORE II>8% and possible femoral access was 99%. The abnormal cardiac uptake rate on BS was 7% (95% confidence interval: 2-12%); 86% of these patients were male. The RAISE (remodelling, age, injury, system and electrical) score, indicative of ATTR-CM risk, was higher in case of positive BS (P=0.04). Patients with positive BS were older and exhibited wider QRS complexes on electrocardiography (P=0.003), a higher frequency of reduced LVEF (57% vs. 17%), impaired basal LV strain (P=0.02) and a lower voltage/mass ratio (P=0.01). History of pacemaker implantation before TAVI was higher in the positive BS group (P=0.0004) and remained the only statistically significant factor after adjustment using the Holm-Bonferroni method. One-year survival of patients with positive BS did not differ from that of patients with isolated AS. CONCLUSIONS: Prevalence of ATTR-CM in patients treated with TAVI, underscoring the need for continued surveillance for potential development of ATTR-CM after TAVI. Caution is warranted regarding the 1-year survival because of the lack of study power. Further investigations are needed to define long-term prognosis of AS with ATTR-CM.
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PURPOSE OF REVIEW: Transcatheter Aortic Valve Replacement (TAVR) has become the preferred treatment approach for many patients with symptomatic severe aortic valve stenosis (SsAS), particularly those who are deemed at high surgical risk. However, in low-risk surgical patients (LSRP) with SsAS, the choice between TAVR and surgical aortic valve replacement (SAVR) is often a matter of debate and depends on several clinical and anatomical considerations. RECENT FINDINGS: Midterm data show similar clinical outcomes and durability of TAVR and SAVR bioprosthetic valves in LRSP. Data on long term durability and outcomes of TAVR in LRSP remains scarce. Both TAVR and SAVR are reasonable options in LRSP with SsAS. Nevertheless, many of these LRSP are expected to outlive their bioprosthetic valves and planning for the second aortic valve replacement should begin at the time of the index procedure with special consideration for coronary re-access, risk for coronary obstruction, and prothesis patient mismatch.
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BACKGROUND: Studies in paradoxical low-flow low-gradient aortic stenosis (PLFAS) have demonstrated conflicting outcomes with variable survival advantage from aortic valve replacement (AVR). PLFAS is a heterogeneous composition of patients with uncertainty regarding true stenosis severity that continues to confound decision-making for AVR. OBJECTIVES: The purpose of this study was to investigate the utility of the Doppler acceleration (AT) to ejection (ET) time ratio (AT:ET) for prediction of prognosis and benefit from AVR in undifferentiated PLFAS. METHODS: Patients with echocardiographic findings of PLFAS (aortic valve area <1.0 cm2 or indexed aortic valve area <0.6 cm2/m2, mean gradient <40 mm Hg, indexed stroke volume <35 mL/m2, and left ventricular ejection fraction ≥50%) were identified and grouped according to an AT:ET cutoff of 0.35. The primary outcome was a 5-year composite of cardiac mortality or AVR. Secondary outcomes included the individual components of the primary endpoint and all-cause mortality at 5 years. Effect of AVR was analyzed in the AT:ET <0.35 and ≥0.35 groups. RESULTS: A total of 171 PLFAS patients (median age 77.0 years, 57% women) were followed for a median of 8.9 years. AT:ET ≥0.35 was an independent predictor of the primary outcome (HR: 4.77 [95% CI: 2.94-7.75]; P < 0.001) with incremental value over standard indices of stenosis severity (net reclassification improvement: 0.57 [95% CI: 0.14-0.84]). AT:ET ≥0.35 also remained predictive of increased cardiac death (HR: 2.91 [95% CI: 1.47-5.76]; P = 0.002) and AVR (HR: 8.45 [95% CI: 4.16-17.1]; P < 0.001), respectively, following competing risk analysis. No difference in all-cause mortality was observed. AVR in the AT:ET ≥0.35 group was associated with significant reductions in 5-year cardiac (HR: 0.09 [95% CI: 0.02-0.36]; P < 0.001) and all-cause mortality (HR: 0.16 [95% CI: 0.07-0.38]; P < 0.001). No improvement in survival from AVR was demonstrated in AT:ET <0.35 patients. CONCLUSIONS: AT:ET ≥0.35 in PLFAS predicts poorer outcomes and/or need for AVR. In undifferentiated PLFAS patients, AT:ET may have a potential role in improving patient selection for prognostic AVR.
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BACKGROUND: Adverse outcomes from moderate aortic stenosis (AS) may be caused by progression to severe AS or by the effects of comorbidities. In the absence of randomized trial evidence favoring aortic valve replacement (AVR) in patients with moderate AS, phenotyping patients according to risk may assist decision making. OBJECTIVES: This study sought to identify and validate clusters of moderate AS that may be used to guide patient management. METHODS: Unsupervised clustering algorithms were applied to demographics, comorbidities, and echocardiographic parameters in a training data set in patients with moderate AS (n = 2,469). External validation was obtained by assigning the defined clusters to an independent group with moderate AS (n = 1,358). The primary outcome, a composite of cardiac death, heart failure hospitalization, or aortic valve (AV) intervention after 5 years, was assessed between clusters in both data sets. RESULTS: Four distinct clusters-cardiovascular (CV)-comorbid, low-flow, calcified AV, and low-risk-with significant outcomes (log-rank P < 0.0001 in both data sets) were identified and replicated. The highest risk was in the CV-comorbid cluster (validation HR: 2.00 [95% CI: 1.54-2.59]; P < 0.001). The effect of AVR on cardiac death differed among the clusters. There was a significantly lower rate of outcomes after AVR in the calcified AV cluster (validation HR: 0.21 [95% CI: 0.08-0.57]; P = 0.002), but no significant effect on outcomes in the other 3 clusters. These analyses were limited by the low rate of AVR. CONCLUSIONS: Moderate AS has several phenotypes, and multiple comorbidities are the key drivers of adverse outcomes in patients with moderate AS. Outcomes of patients with noncalcified moderate AS were not altered by AVR in these groups. Careful attention to subgroups of moderate AS may be important to define treatable risk.
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BACKGROUND: The coexistence of mitral regurgitation (MR) and severe aortic stenosis (AS) has been associated with worse outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Herein, the aim was to assess the etiology and degree of MR in an unselected TAVI population and investigate the impact of MR reduction at mid-term follow-up. METHODS: Patients subjected to TAVI as a treatment for severe AS in a single center were retrospectively analyzed. The primary endpoint was the MR reduction after TAVI. The secondary endpoint was all-cause mortality and heart failure hospitalization at a 3-year follow-up. RESULTS: Patients undergoing TAVI (n = 283) in the years 2017-2019 were screened for the presence of hemodynamically significant MR. Sixty-nine subjects (24.4%) with severe (16, 23.2%) and moderate (53, 76.8%) MR were included. The primary MR was predominant (39 subjects, 56.5%). The median age of the patients was 82 years. MR improved in 25 patients (36.2%, p < 0.001). Baseline severe MR was more prone to reduce (8 subjects, 50%) than moderate (17 subjects, 32.1%, p = 0.04). The primary MR improved in 14 patients (35.9%), while secondary in 11 patients (36.7%, p = 1). Patients showing MR reduction had lower mortality (8 vs. 29.55%, p = 0.047) and were less frequently hospitalized (20 vs. 45.45%, p = 0.03) at 3-year follow-up. CONCLUSIONS: Hemodynamically significant MR improves after TAVI regardless of its etiology. Moreover, MR reduction after TAVI is associated with better clinical outcomes.
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Aortic stenosis has become the most prevalent valvular disease with increasing life expectancy and the ageing of the population, representing a significant clinical burden for health care providers. Its treatment has been revolutionized by transcatheter aortic valve replacement (TAVR) as a safe and minimally invasive option for elderly patients. Left ventricular (LV) functional measurement is of particular importance before TAVR, however, increased afterload significantly influences the conventional echocardiographic parameters. Non-invasive myocardial work examines myocardial deformation in the context of instantaneous LV pressure, thus, it might be a more reliable measure of LV function. Accordingly, we aimed to study non-invasive myocardial work and its relationship with functional outcome following TAVR.We enrolled 90 TAVR candidates (80 [75-84] years; 44% female). Using echocardiography, we quantified ejection fraction (EF), global longitudinal strain (GLS), global myocardial work index (GWI) and global constructive work (GCW) before and 12 months after the procedure. Serum NT-proBNP levels were also measured. EF did not change (52.6 ± 13.1 vs. 54.2 ± 10.5%; p = 0.199), while GLS increased (-13.5 ± 4.6 vs. -15.2 ± 3.8%; p < 0.001). GWI decreased (1913 ± 799 vs. 1654 ± 613 mmHg%; p < 0.001) and so did GCW (2365 ± 851 vs. 2177 ± 652 mmHg%; p = 0.018). History of atrial fibrillation (AF) (ß = 0.349) and preprocedural GCW (ß = -0.238) were independent predictors of postprocedural NT-proBNP (p < 0.001).GLS, GWI and GCW changed after TAVR while there was no alteration in EF. The preprocedural GCW and history of AF were independent predictors of postprocedural NT-proBNP. Accordingly, myocardial work indices may help patient selection and the prediction of the functional outcome in this population.
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BACKGROUND: Aortic valve stenosis (AS) is the most prevalent valvular heart disease and is associated with a significant increase in mortality. AS has been shown to be linked with numerous coagulation system abnormalities, including increased fibrin deposition on the stenotic aortic valves. Transcatheter aortic valve implantation (TAVI) is the primary treatment method for patients at high surgical risk. OBJECTIVES: The aim of the study was to assess the impact of treating severe AS with TAVI on thrombin generation and clot lysis time (CLT). METHODS: We studied 135 symptomatic AS patients recommended for TAVI by the local Heart Team. All measurements were performed before and 5-7 days after TAVI. Alongside clinical assessment and echocardiographic analysis, we assessed clot lysis time (CLT) and thrombin generation parameters, including lag time, peak thrombin generation, time to peak thrombin generation (ttPeak), and endogenous thrombin potential (ETP). RESULTS: 70 patients were included in the final analysis. After TAVI, there was a significant 9% reduction in CLT despite a 12% increase in fibrinogen concentration. We observed significant increase in lag time and ttPeak (20% and 12%, respectively), and 13% decrease in peak thrombin concentration compared to pre-procedural levels. Multivariable linear regression analysis demonstrated that baseline CLT and C-reactive protein (CRP) levels were independent predictors of significant reduction in mean aortic gradient, defined as TAVI procedure success. CONCLUSIONS: CLT and peak thrombin concentration decreased, while Lag time and ttPeak increased significantly after TAVI. Multivariable linear regression analysis demonstrated CLT and CRP levels as independent predictors of achieving a reduction in mean aortic gradient, defining TAVI procedure success.