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Data on systemic inflammatory response syndrome (SIRS) after transcatheter aortic valve implantation (TAVI) are scarce and limited to small cohorts. We aimed to investigate its incidence and mid-term impact in a large cohort of TAVI patients. From January 2018 to December 2020, 717 patients with severe aortic valve stenosis undergoing TAVI were included. SIRS was defined as fulfilling at least two of the following criteria within 48 h from the procedure: leucocyte count >12.0 or <4.0 × 109/l, respiratory rate > 20 breaths per minute or PaCO 2 ≤ 4.3 kPa/32 mmHg, heart rate > 90 beats per minute and temperature > 38.0 °C or <36.0 °C. Clinical endpoints were 1-year rehospitalization for chronic heart failure (CHF) and 2-years all-cause mortality. Event rates during follow-up were calculated as Kaplan-Meier estimates. SIRS developed in 56.3 % (404/717) of patients after TAVI. SIRS occurred more frequently in patients with post-dilatation (SIRS 34.7 % (140/404) vs. no SIRS 23.3 % (73/313); p < 0.001) and major vascular complications (SIRS 16.1 % (65/404) vs. no SIRS 8.6 % (27/313); p = 0.004). Further, ICU days were more in patients who developed SIRS (SIRS 1.56 ± 1.50 days vs. no SIRS 1.22 ± 1.02 days; p = 0.001). At 2-years, all-cause mortality in the entire population was 23.9 %. However, there was no difference in CHF at 1-year (5.9 % vs. 4.1 %; log-rank = 0.347) nor in all-cause mortality at 2-years (22.0 % vs. 26.2 %; log-rank = 0.690) between the groups. SIRS is a common finding after TAVI, which may prolong hospital stay but is without effect on mortality during 2-years follow-up. • SIRS is a common finding after TAVI, occurring in more than half of patients. • SIRS occurs more often in patients with post-dilatation and major vascular complications. • Inflammatory markers after TAVI increase, irrespective of SIRS development. • The occurrence of SIRS after TAVI is without effect on 2-years mortality. [ABSTRACT FROM AUTHOR]

Direct comparisons of latest-generation balloon-expandable versus self-expanding transcatheter heart valves (THV) are scarce. To compare outcomes after transcatheter aortic valve replacement (TAVR) with SAPIEN 3 Ultra (Ultra) versus Evolut R or Pro (Evolut) THVs. 1612 consecutive patients undergoing TAVR with either Ultra (n = 616) or Evolut (n = 996) were included. After propensity score matching (PSM), 467 and 205 matched pairs were identified in the entire cohort and with latest-generation THVs, respectively. Outcomes were investigated up to 30 days after TAVR. After PSM, baseline characteristics were comparable in the entire cohort (n = 934). Device success (92.7% vs. 87.6%; p = 0.011) and need for permanent pacemaker implantation (PPI) (15.2% vs. 8.4%; p = 0.002) were higher for Evolut compared with Ultra. Elevated gradients (≥20 mm Hg) were less frequent (1.6% vs. 10.4%; p < 0.001), whereas rates of ≥ moderate paravalvular leakage (PVL II+) were more frequent for Evolut compared with Ultra (3.7% vs. 1.3%; p = 0.019). With latest-generation THVs (n = 410), device success was comparable (93.2% vs. 89.8%; p = 0.216), whereas the need for PPI was higher for Evolut Pro compared with Ultra (15.6% vs. 9.8%; p = 0.075). Elevated gradients were less frequent (0% vs. 8%; p < 0.001), whereas rates of PVL II+ were more frequent for Evolut compared with Ultra (5.4% vs. 1.5%; p = 0.028). Device success rates were high with both THV platforms with low rates of adverse events up to 30 days after TAVR. Compared with Ultra, Evolut was associated with higher pacemaker rates as well as PVL II+, but with less elevated gradients. • Large, multicenter, propensity-matched comparison of latest-generation SAPIEN 3 Ultra versus Evolut THVs • High device success rates with both THV platforms with low rates of adverse events up to 30 days after TAVR • Use of Evolut was associated with higher permanent pacemaker rates as well as moderate or severe paravalvular leakage, but with less elevated transprosthetic gradients compared with Ultra [ABSTRACT FROM AUTHOR]

Aim: Psoas muscle cross-sectional area (CSA) is a proposed marker of frailty associated with mortality after transcatheter aortic valve implantation (TAVI). We assessed the impact of psoas CSA on medium-term mortality over 5 years in a large cohort, adjusted for pre-procedural variables.Method: This single-centre registry-derived analysis assessed 1,731 consecutive TAVI patients between 2007 and 31 April 2015 with available abdominal computed tomography scans. Sex-stratified, height-adjusted psoas CSA was measured mid-body of the fourth lumbar vertebra. Kaplan-Meier survival distributions across psoas CSA quartiles were compared. Cox and logistic regression models were used to assess baseline variables associated with the primary outcome, which was mortality within 5 years.Results: Median age was 81 years (interquartile range, 77 - 85); 52.5% were women. The primary endpoint occurred in 555 patients over a mean follow-up of 775 days. Lower psoas CSA quartile patients were older, had a lower body mass index, lower creatinine clearance, and lower rates of previous cardiac surgery, with higher rates of diabetes, coronary artery disease, pacemaker, anaemia, hypoalbuminaemia, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE). Unadjusted survival by psoas CSA quartile was significantly different in men (log rank p=0.041) but not women (p=0.099). In Bonferroni-adjusted multivariate analysis, psoas CSA quartiles were not significantly associated with mortality. Hypoalbuminaemia (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.53 - 2.87 [p<0.001]) and increasing age (HR, 1.03 per year; 95% CI, 1.01 - 1.05 [p=0.002]) were associated with increased risk; female sex (HR, 0.63; 95% CI 0.51 - 0.78 [p<0.001]), and hypercholesterolaemia (HR, 0.67; 95%, CI 0.54 0.83 [p<0.001]) with reduced risk.Conclusions: Psoas CSA was not significantly associated with mortality after adjusting for pre-procedural variables. Hypoalbuminaemia, sex, hypercholesterolaemia, and age were significantly associated with mortality after TAVI. [ABSTRACT FROM AUTHOR]

Purpose: Elevated carbohydrate antigen 125 (CA125) predicts adverse outcome after transcatheter aortic valve implantation (TAVI). While known underlying pathophysiological mechanisms of elevated CA125 include serosal effusions and inflammatory stimuli, clinical determinants associated with elevated CA125 in patients referred for TAVI remain unknown. Therefore, we investigated clinical, laboratory and echocardiographic determinants of elevated CA125 in patients with severe aortic valve stenosis referred for TAVI. Methods: This study includes 650 patients with severe aortic stenosis referred for TAVI. Baseline CA125 was determined by an immunoassay and dichotomized (elevated versus normal) based on the manufacturer cutoff value (>35 U/mL). Results: CA125 elevation was present in 28% (181/650). Patients with elevated CA125 had an overall worse clinical profile and were more symptomatic with a higher rate of NYHA class III/IV (80% versus 58%; p < 0.001). In a multivariate analysis, independent predictors of elevated CA125 were New York Heart Association (NYHA) class, baseline hemoglobin, C-reactive protein (CRP), left ventricular ejection fraction and severe tricuspid regurgitation. Conclusion: Elevated CA125 levels in patients referred for TAVI summarize a subset of patients with an overall worse clinical profile who are more symptomatic. [ABSTRACT FROM AUTHOR]

Introduction Anemia is frequent in patients undergoing transcatheter aortic valve implantation (TAVI) with a strong negative prognostic impact. The prevalence and prognosis of anemia and separately of iron-deficiency anemia in contemporary patients are unclear. Methods and results In total, 549 consecutive patients undergoing transfemoral TAVI were included in the single-center study. Baseline anemia was defined as a hemoglobin level < 13 g/dL in men and < 12 g/dL in women. In an unselected subgroup of anemic patients (n = 115), a complete iron status was obtained and anemia was classified as iron-deficiency versus non-iron-deficiency. The primary endpoint was death or re-hospitalization for worsening heart failure within one year after TAVI. Anemia was present in 45% (249/549) of the population and was significantly associated with a higher rate of the primary endpoint (25% (63/249) vs. 8% (25/300); p < 0.001). In a multivariable model adjusted for variables associated with the primary endpoint, baseline anemia was an independent predictor of the primary endpoint (hazard ratio 2.81, 95% confidence interval [1.69–4.67]; p < 0.001). Iron-deficiency anemia was present in 79% (91/115) of the subgroup and the rate of the primary endpoint was comparable to non-iron-deficiency anemia (31% (28/91) vs. 21% (5/24); p = 0.338). Conclusion In contemporary TAVI patients, anemia remains a common comorbidity and independently predicts adverse outcome. In an unselected subgroup of anemic patients, iron-deficiency was common and had similar clinical outcome compared to non-iron-deficiency. Whether correction of iron-deficiency anemia impacts prognosis remains to be investigated. [ABSTRACT FROM AUTHOR]

Background Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. Methods Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. Results A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P <.001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P <.001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P <.001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P =.033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P <.001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P =.697). Conclusions Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up. [ABSTRACT FROM AUTHOR]

Background Echocardiography is the primary imaging modality for diagnosis of infective endocarditis (IE) in prosthetic valve endocarditis (PVE) including IE after transcatheter aortic valve implantation (TAVI). This study aimed to evaluate the characteristics and clinical outcomes of patients with absent compared with evident echocardiographic signs of TAVI-IE. Methods Patients with definite TAVI-IE derived from the Infectious Endocarditis after TAVI International Registry were investigated comparing those with absent and evident echocardiographic signs of IE defined as vegetation, abscess, pseudo-aneurysm, intracardiac fistula, or valvular perforation or aneurysm. Results Among 578 patients, 87 (15.1%) and 491 (84.9%) had absent (IE-neg) and evident (IE-pos) echocardiographic signs of IE, respectively. IE-neg were more often treated via a transfemoral access with a self-expanding device and had higher rates of peri-interventional complications (eg, stroke, major vascular complications) during the TAVI procedure (P <.05 for all). IE-neg had higher rates of IE caused by Staphylococcus aureus (33.7% vs 23.2%; P =.038) and enterococci (37.2% vs 23.8%; P =.009) but lower rates of coagulase-negative staphylococci (4.7% vs 20.0%, P =.001). IE-neg was associated with the same dismal prognosis for in-hospital mortality in a multivariate binary regression analysis (odds ratio: 1.51; 95% confidence interval [CI]:.55–4.12) as well as a for 1-year mortality in Cox regression analysis (hazard ratio: 1.10; 95% CI:.67–1.80). Conclusions Even with negative echocardiographic imaging, patients who have undergone TAVI and presenting with positive blood cultures and symptoms of infection are a high-risk patient group having a reasonable suspicion of IE and the need for an early treatment initiation. [ABSTRACT FROM AUTHOR]

Background Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients. Methods This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53–421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula. Results A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27–3.41; P  = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57–4.69; P  < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P  < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (p adj < 0.05 for all). Conclusions PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment of patients developing infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is uncertain.Objectives: The goal of this study was to investigate the clinical characteristics and outcomes of patients with TAVI-IE treated with cardiac surgery and antibiotics (IE-CS) compared with patients treated with antibiotics alone (IE-AB).Methods: Crude and inverse probability of treatment weighting analyses were applied for the treatment effect of cardiac surgery vs medical therapy on 1-year all-cause mortality in patients with definite TAVI-IE. The study used data from the Infectious Endocarditis after TAVI International Registry.Results: Among 584 patients, 111 patients (19%) were treated with IE-CS and 473 patients (81%) with IE-AB. Compared with IE-AB, IE-CS was not associated with a lower in-hospital mortality (HRunadj: 0.85; 95% CI: 0.58-1.25) and 1-year all-cause mortality (HRunadj: 0.88; 95% CI: 0.64-1.22) in the crude cohort. After adjusting for selection and immortal time bias, IE-CS compared with IE-AB was also not associated with lower mortality rates for in-hospital mortality (HRadj: 0.92; 95% CI: 0.80-1.05) and 1-year all-cause mortality (HRadj: 0.95; 95% CI: 0.84-1.07). Results remained similar when patients with and without TAVI prosthesis involvement were analyzed separately. Predictors for in-hospital and 1-year all-cause mortality included logistic EuroSCORE I, Staphylococcus aureus, acute renal failure, persistent bacteremia, and septic shock.Conclusions: In this registry, the majority of patients with TAVI-IE were treated with antibiotics alone. Cardiac surgery was not associated with an improved all-cause in-hospital or 1-year mortality. The high mortality of patients with TAVI-IE was strongly linked to patients' characteristics, pathogen, and IE-related complications. [ABSTRACT FROM AUTHOR]

ACURATE neo2 (Neo2) implantation is performed after systematic Balloon Aortic Valvuloplasty (BAV) in most patients. No reports exist about the feasibility and safety of direct Neo2 transcatheter aortic valve implantation (TAVI) in comparison to the standard practice. We aimed to identify the patients' baseline anatomical characteristics, procedural, and early post-procedural outcomes in patients treated using Neo2 with and without BAV. This is a retrospective multicentre analysis of 499 patients with severe aortic stenosis who underwent TAVI using Neo2. The comparison was done according to the performance or omission of BAV. Echocardiography and computed tomography were analysed by an independent Core Lab. Propensity score matching (PSM) was performed based on the annular diameter and AV calcium volume, which identified 84 matched pairs. Among the cohort included, 391 (78%) patients received BAV (BAV-yes) and 108 (22%) were not attempted (BAV-no or Direct TAVI). Patients in BAV-no cohort had smaller annular diameter (22.6 vs 23.4 mm; p < 0.001) and lower calcium volume (163 vs 581 mm3; p < 0.001) compared to BAV-yes cohort. In the matched cohort, VARC-3 device technical success was similar (95%) and all other outcome measures were statistically comparable between cohorts. Direct TAVI using ACURATEneo2 without pre-TAVI balloon aortic valvuloplasty in patients with mild or less valve calcifications might be feasible and associated with comparable early outcomes compared to patients with similar anatomical features undergoing systematic balloon valvuloplasty. • ACURATEneo2 implantation is performed after systematic balloon aortic valvuloplasty with a rate higher than the contemporary devices • Implantation of ACURATEneo2 without balloon aortic valvuloplasty is not investigated yet. • Direct implantation of ACURATEneo2 in patients with aortic stenosis and mild valve calcifications showed a high rate of technical success • Procedural, in-hospital clinical outcomes and hemodynamic outcomes were comparable between the two study cohorts [ABSTRACT FROM AUTHOR]

Background Procedural improvements combined with the contemporary clinical profile of patients undergoing transcatheter aortic valve replacement (TAVR) may have influenced the incidence and outcomes of infective endocarditis (IE) following TAVR. We aimed to determine the temporal trends, characteristics, and outcomes of IE post-TAVR. Methods Observational study including 552 patients presenting definite IE post-TAVR. Patients were divided in 2 groups according to the timing of TAVR (historical cohort [HC]: before 2014; contemporary cohort [CC]: after 2014). Results Overall incidence rates of IE were similar in both cohorts (CC vs HC: 5.45 vs 6.52 per 1000 person-years; P  = .12), but the rate of early IE was lower in the CC (2.29‰ vs 4.89‰, P  < .001). Enterococci were the most frequent microorganism. Most patients presented complicated IE (CC: 67.7%; HC: 69.6%; P  = .66), but the rate of surgical treatment remained low (CC: 20.7%; HC: 17.3%; P  = .32). The CC exhibited lower rates of in-hospital acute kidney injury (35.1% vs 44.6%; P  = .036) and in-hospital (26.6% vs 36.4%; P  = .016) and 1-year (37.8% vs 53.5%; P  < .001) mortality. Higher logistic EuroScore, Staphylococcus aureus etiology, and complications (stroke, heart failure, and acute renal failure) were associated with in-hospital mortality in multivariable analyses (P  < .05 for all). Conclusions Although overall IE incidence has remained stable, the incidence of early IE has declined in recent years. The microorganism, high rate of complications, and very low rate of surgical treatment remained similar. In-hospital and 1-year mortality rates were high but progressively decreased over time. [ABSTRACT FROM AUTHOR]

The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known. We assessed the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive management. This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomized to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding (both endpoints assessed at 12 months). There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR] = 1.15; 95% confidence interval [CI] 0.76–1.75; P = 0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR = 1.44 [1.10–1.87]; P = 0.007; P for interaction = 0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR = 0.81 [0.49–1.35]; P = 0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR = 1.38 [0.94–2.01]; P = 0.097). In patients with ACS undergoing an invasive management strategy, the smoking status did not significantly interact with the relative treatment effect of ticagrelor vs. prasugrel. NCT01944800 • In ACS patients, ticagrelor and prasugrel showed similar efficacy regardless of smoking status. • Bleeding risk was comparable between ticagrelor and prasugrel in smokers and nonsmokers. • Smoking status does not interfere with the relative treatment effect of ticagrelor vs. prasugrel. [ABSTRACT FROM AUTHOR]

Background: Stroke is one of the most common and potentially disabling complications of infective endocarditis (IE). However, scarce data exist about stroke complicating IE after transcatheter aortic valve replacement (TAVR).Objectives: The purpose of this study was to determine the incidence, risk factors, clinical characteristics, management, and outcomes of patients with definite IE after TAVR complicated by stroke during index IE hospitalization.Methods: Data from the Infectious Endocarditis after TAVR International Registry (including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries) was analyzed. Patients were divided into two groups according to stroke occurrence during IE admission (stroke [S-IE] vs. no stroke [NS-IE]).Results: A total of 57 (10%) patients had a stroke during IE hospitalization, with no differences in causative microorganism between groups. S-IE patients exhibited higher rates of acute renal failure, systemic embolization, and persistent bacteremia (p < 0.05 for all). Previous stroke before IE, residual aortic regurgitation ≥moderate after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size >8 mm were associated with a higher risk of stroke during the index IE hospitalization (p < 0.05 for all). Stroke rate in patients with no risk factors was 3.1% and increased up to 60% in the presence of >3 risk factors. S-IE patients had higher rates of in-hospital mortality (54.4% vs. 28.7%; p < 0.001) and overall mortality at 1 year (66.3% vs. 45.6%; p < 0.001). Surgical treatment was not associated with improved outcomes in S-IE patients (in-hospital mortality: 46.2% in surgical vs. 58.1% in no surgical treatment; p = 0.47).Conclusions: Stroke occurred in 1 of 10 patients with IE post-TAVR. A history of stroke, short time between TAVR and IE, vegetation size, valve prosthesis type, and residual aortic regurgitation determined an increased risk. The occurrence of stroke was associated with increased in-hospital and 1-year mortality rates, and surgical treatment failed to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS. Highlights • The Lipoprotein (a) risk variant, LPA shows a robust association with risk of AVS, independent of CAD. • The effect size of the LPA risk allele is higher in patients without concomitant CAD. • High Lp(a) levels are associated with younger age of need for TAVR, especially in those without CAD. • The strongest CAD risk allele at 9p21 is not associated with risk of AVS. [ABSTRACT FROM AUTHOR]