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Aims: Although dual antiplatelet therapy with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remains challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI)., Methods and Results: PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA, USA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6 ± 4.0 years, females 44%) were included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4 ± 32.1 vs. 30.4 ± 39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; P for non-inferiority = 0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29 ± 312.36 ng/mL vs. 579.57 ± 351.73 ng/mL, P = 0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg., Conclusion: Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) has recently introduced a consensus document that outlines risk factors to identify high bleeding risk (HBR) in patients undergoing transcatheter aortic valve replacement (TAVR). The objective of the present study was to evaluate the prevalence and predictive value of the VARC-HBR definition in a contemporary, large-scale TAVR population. Methods: Multicenter study including 10,449 patients undergoing TAVR. Based on consensus, twenty-one clinical and laboratory criteria were identified and classified as major or minor. Patients were stratified as at low, moderate, high, and very high bleeding risk according to VARC-HBR definition. The primary endpoint was the rate of BARC type 3 or 5 bleeding at 1 year, defined as the composite of peri-procedural (within 30 days) or late (after 30 days) bleeding. Results: Patients with at least one VARC-HBR criterion (n=9,267, 88.7%) had a higher risk of BARC 3 or 5 bleeding, proportional to the severity of risk assessment (10.8%, 16.1%, and 24.6% for moderate, high, and very high-risk groups, respectively). However, a comparable rate of bleeding events was observed in the low-risk and moderate-risk groups. The area under ROC curve was 0.58. Patients with VARC-HBR criteria also exhibited a gradual increase in 1-year all-cause mortality, with an up to 2-fold increased mortality risk for high and very high-risk groups (HR: 1.33, 95% CI: 1.04-1.70; and HR: 1.97, 95% CI: 1.53-2.53, respectively). Conclusions: The VARC-HBR consensus offered a pragmatic approach to guide bleeding risk stratification in TAVR. The results of the present study would support the predictive validity of the newly definition and promote its application in clinical practice to minimize bleeding risk and improve patient outcomes.

Importance: Heart failure (HF) and aortic stenosis (AS) frequently coexist, presenting a complex clinical challenge due to their intertwined pathophysiology and associated high morbidity and mortality. Despite numerous advancements in transcatheter and surgical aortic valve replacement (AVR), HF decompensation remains the leading cause of cardiac rehospitalization and a major predictor of mortality in patients with AS, before or after AVR. This review aims to provide a comprehensive analysis of the interplay between AS and HF, delving into myocardial changes caused by stenotic insult, the impact of AVR on these changes, and the prevalence and contributing elements of HF before and after AVR., Observations: The prevalence of HF remains high before and after AVR, particularly among patients with left ventricular dysfunction. Increased afterload from AS causes cardiac remodeling, which is initially benign but over time these changes become maladaptive, contributing to HF and increased mortality. The progression of HF is influenced by the degree of reverse cardiac remodeling, which can be affected by comorbid conditions, the hemodynamic performance of the valve prosthesis, and vascular stiffness. Several blood and imaging biomarkers offer insights into underlying AS pathophysiology, serving as mortality predictors and predicting HF in this patient population., Conclusions and Relevance: HF development in AS is multifactorial and its link to left ventricular dysfunction is a complex process. Delineating the determinants of HF admissions in AS is crucial for identifying individuals at high risk. Identifying the early signs of left ventricular decompensation by using surrogate markers may be the key, even before left ventricular function becomes impaired. Translating multimodality imaging techniques and biomarkers into routine clinical practice for evaluating cardiac damage and integrating these markers with patient and procedural factors that affect HF before and after AVR can facilitate timely intervention, minimizing the likelihood of HF progression and influencing future guidelines.

Purpose: The prognostic significance of noninvasive myocardial work (MW) indices in patients undergoing transcatheter aortic valve implantation (TAVI) has not been adequately examined., Methods: We retrospectively selected 88 consecutive patients (mean age 79.9 ± 6.4 years, 40% males) with severe aortic stenosis scheduled for TAVI enrolled in the EffecTAVI registry. Exclusion criteria were prior valve surgery, atrial fibrillation, and left bundle branch block (LBBB) at baseline. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were measured by echocardiography at baseline and at 30 days. Accuracy of the noninvasive measures was assessed by invasive evaluation of MW., Results: In the overall population, a significant reduction in GWI (2406 ± 567 vs. 2063 ± 515 mmHg% before and after TAVI respectively, P  < 0.001), GCW (2783 ± 616 vs. 2380 ± 495 mmHg%, P  < 0.001) and GWW (238 ± 203 vs. 186 ± 135 mmHg%, P  = 0.015) was observed at 30 days after TAVI. GWE improved only in patients who did not develop left ventricular dyssynchrony due to new-onset LBBB or pacemaker implantation following TAVI. In a multivariable Cox-regression analysis, GWE after TAVI (hazard ratio 0.892, 95% confidence interval 0.81-0.97; P  = 0.011) was the strongest predictor of adverse events (a composite of all-cause death, worsening of dyspnea, or rehospitalization for cardiovascular events) at 1-year follow-up., Conclusions: TAVI results in significant changes in MW indices, including an early decrease in GWI, GCW and GWW, and an improvement in GWE in patients without left ventricle dyssynchrony. A GWE equal or less than 92% at 30 days is indicative of poor clinical outcomes at 1 year., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The Valve Academic Research Consortium (VARC)-3 definition for neurologic events after transcatheter aortic valve replacement (TAVR) lacks clinical validation., Objectives: This study sought to determine the incidence, predictors, and clinical impact of neurologic events following TAVR as defined by VARC-3 criteria., Methods: This was a multicenter study including 2,924 patients with severe aortic stenosis undergoing TAVR. Based on Neurologic Academic Research Consortium (NeuroARC) classification, neurologic events were classified as NeuroARC type 1 (stroke), NeuroARC type 2 (covert central nervous system injury), and NeuroARC type 3 (transient ischemic attack and delirium). Baseline, procedural, and follow-up data were prospectively collected in a dedicated database., Results: After a median follow-up of 13 (7-37) months, neurologic events occurred in 471 patients (16.1%), NeuroARC type 1, 2, and 3 in 37.4%, 4.7%, and 58.0% of cases, respectively, and the majority (58.6%) were periprocedural. Advanced age, chronic kidney disease, atrial fibrillation, major vascular complications, and in-hospital bleeding determined an increased risk of periprocedural events (P < 0.03 for all). Neurologic events occurring during the periprocedural time frame were independently associated with a substantial increase in mortality at 1 year after the intervention (HR: 1.91; 95% CI: 1.23-2.97; P = 0.004). However, although NeuroARC type 1 was associated with an increased mortality risk (IRR: 3.38; 95% CI: 2.30-5.56; P < 0.001 and IRR: 21.7; 95% CI: 9.63-49.1; P < 0.001 for ischemic and hemorrhagic stroke, respectively), the occurrence of NeuroARC type 3 events had no impact on mortality., Conclusions: Neurologic events after TAVR were associated with poorer short- and long-term survival. This correlation was related to the type of NeuroARC event defined by the VARC-3 criteria. Given the negative impact on clinical outcomes, every attempt should be made to reduce the risk of neurologic complications after TAVR., Competing Interests: Funding Support and Author Disclosures Dr Cepas-Guillén has received a grant from the Fundación Alfonso Martín Escudero. Dr Rodés-Cabau has received institutional research grants and speaker/consultant fees from Edwards Lifesciences and Medtronic, and holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Interventions (Laval University). All other authors have reported that they have no relationships relevant to the contents of this paper., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background . Lower extremity peripheral artery disease (LEPAD) frequently coexists with coronary artery disease (CAD) in patients with multisite vascular disease (MVD). While percutaneous revascularization is well-established for both LEPAD and CAD, limited evidence exists for patients eligible for both procedures. Specifically, the feasibility of concomitant LEPAD and CAD percutaneous revascularization remains unknown. Objectives . To compare the efficacy and safety of concomitant coronary and lower extremity elective percutaneous revascularization. Methods . Between 2012 and 2021, we included 135 patients in an observational, retrospective single-center registry. The population was stratified into two groups: 45 patients (concomitant group) underwent simultaneous coronary and peripheral percutaneous interventions, and 90 patients (deferred group) underwent two separate procedures within one year. The primary efficacy endpoint was major adverse cardiovascular events (MACE) at one year, while the primary safety endpoint was in-hospital contrast-induced nephropathy (CIN). Results . Study groups were well-balanced in baseline characteristics. In terms of coronary features, the concomitant revascularization group more often underwent single-vessel percutaneous coronary intervention (PCI), while the deferred group had multivessel PCI with diffuse coronary disease. No differences were detected in the number of LEPAD lesions between groups. For the primary efficacy endpoint, the incidence of MACE at one year was 37.8% in the concomitant group vs. 34.4% in the deferred group (HR 1.20, 95% CI 0.64-2.10; p = 0.61). No significant differences were found in CIN occurrence between the concomitant and deferred groups (11.1% vs. 8.9%; OR 1.30; 95% CI 0.36-4.21; p = 0.68). Conclusions . Multisite vascular disease patients eligible for CAD and LEPAD percutaneous revascularization exhibited a high cardiovascular risk profile with diffuse multivessel coronary and lower extremity disease. Our study suggests the efficacy and safety of concomitant coronary and lower extremity percutaneous revascularization based on one-year MACE incidence and in-hospital CIN. However, dedicated studies are warranted to confirm the short- and long-term outcomes of the concomitant revascularization strategy.

Background: Transcarotid transcatheter aortic valve replacement (TC-TAVR) has emerged as an alternative access route for transcatheter aortic valve replacement (TAVR). However, scarce data exist on long-term outcomes following TC-TAVR. This study aimed to evaluate clinical outcomes at 5 years after TC-TAVR., Methods: A total of 110 consecutive patients who underwent TC-TAVR were included. Baseline, procedural, and follow-up data were collected prospectively in a dedicated database. The primary endpoint was the incidence of a composite outcome of all-cause mortality, stroke, and repeat hospitalization at 5-year follow-up. Echocardiography results, New York Heart Association (NYHA) class, and quality of life (QoL) as assessed with the EuroQol visual analog scale (EQ-VAS) were examined over the 5-year follow-up., Results: The median patient age was 77 years (interquartile range [IQR], 72-82.2 years), 42.3% were women, and the median Society of Thoracic Surgeons (STS) risk score was 5.02% (IQR, 3.4%-7.5%). The incidence of the composite primary endpoint was 54.5%. Death from any cause occurred in 45.6% of patients (11.9 per 100 patient-years); stroke in 8.2% (1.9 per 100 patient-years); disabling stroke in 2.7% (0.7 per 100 patient-years); and rehospitalization in 27.2%. The improvements in valve hemodynamics, NYHA class, and EQ-VAS following the procedure persisted at 5-year follow-up (P < .001). The incidence of bioprosthetic valve failure was 0.9%., Conclusions: About half of the moderate-to high-risk patients undergoing TC-TAVR survived with no major cardiovascular events at the 5-year follow-up. The yearly incidence of stroke events was low, and early improvements in valve hemodynamics, functional status, and QoL persisted at 5 years. These results suggest the long-term safety and efficacy of TC-TAVR and would support this approach as an alternative to surgery in non-transfemoral candidates., Competing Interests: Conflict of Interest Statement Dr Rodés-Cabau has received institutional research grants and consultant/speaker fees from Edwards Lifesciences and Medtronic, and holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Interventions (Laval University). Dr del Portillo has received a scholarship from “Fundación Cardioinfantil-Instituto de Cardiología” and “Colfuturo” (Colombia). Dr Mas-Peiro and Dr Cepas-Guillén have received research grants from the “Fundación Alfonso Martín Escudero” (Madrid, Spain). The rest of authors did not report any potential conflict of interest relevant to the content of this manuscript. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Valve oversizing has been associated with reduced paravalvular leaks (PVL) and valve migration risk. However, no optimal cut-off oversizing value has been defined for the Evolut system (Medtronic). The aim of this study was to assess the relationship between the degree of oversizing and moderate-to-severe PVL and determine the optimal oversizing cut-off value., Methods: We conducted a multicenter study that included 740 consecutive patients with multidetector computed tomography (CT) data. Valve size was selected according to manufacturer recommendations, with oversizing ranging from 10% to 30%. The primary endpoint was moderate-to-severe PVL., Results: The median age was 84 years (79-87 years), with 58.4% women, and a median EuroSCORE II of 4.1% (2.4-7.3%). Moderate-to-severe PVL was observed in 7.0% of the patients. An inverse relationship was found between oversizing and both PVL (11.3%, 8.6%, 5.4%, and 2.7% for quartiles Q1 to Q4; P = .007) and the need for post-dilation (P = .016). The multivariable analysis showed an association between oversizing and PVL (OR: 0.915 for each 1%-increase, P = .002). The optimal oversizing cut-off value to predict PVL was 20%, and PVL was significantly higher in patients with oversizing less than 20% (10.5% vs.4.2%, P less than .001). There were no differences in major clinical events according to the degree of oversizing, and a higher oversizing did not translate into an increased risk of permanent pacemaker (18.4% vs18.3%, P = .976)., Conclusions: In TAVR with the Evolut valve, a higher oversizing was associated with lower rates of moderate-to-severe PVL and a lower need for post-dilation, with no negative impact on procedural and early clinical outcomes. A 20% oversizing threshold could be suggested to reduce PVLs. Further prospective studies are warranted to validate optimal oversizing for this valve system.

Introduction and Objectives: In patients undergoing percutaneous coronary intervention (PCI) in the workup pre-transcatheter aortic valve replacement (TAVR), the clinical impact of coronary revascularization complexity remains unknown. This study sought to examine the impact of PCI complexity on clinical outcomes after TAVR in patients undergoing PCI in the preprocedural workup., Methods: This was a multicenter study including consecutive patients scheduled for TAVR with concomitant significant coronary artery disease. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with 2 stents implanted, total stent length >60mm, or chronic total occlusion. The rates of major adverse cardiac events (MACE), including cardiovascular mortality, myocardial infarction, and coronary revascularization were evaluated., Results: A total of 1550 patients were included, of which 454 (29.3%) underwent complex PCI in the pre-TAVR workup. After a median follow-up period of 2 [1-3] years after TAVR, the incidence of MACE was 9.6 events per 100 patients-years. Complex PCI significantly increased the risk of cardiac death (HR, 1.44; 95%CI, 1.01-2.07), nonperiprocedural myocardial infarction (HR, 1.52; 95%CI, 1.04-2.21), and coronary revascularization (HR, 2.46; 95%CI, 1.44-4.20). In addition, PCI complexity was identified as an independent predictor of MACE after TAVR (HR, 1.31; 95%CI, 1.01-1.71; P=.042)., Conclusions: In TAVR candidates with significant coronary artery disease requiring percutaneous treatment, complex revascularization was associated with a higher risk of MACE. The degree of procedural complexity should be considered a strong determinant of prognosis in the PCI-TAVR population., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: There are scarce data on the factors associated with impaired functional status after transcatheter aortic valve replacement (TAVR) and its clinical impact. This study aimed to determine the incidence, predictors, and prognostic implications of impaired functional class (NYHA class III-IV) following TAVR., Methods: This multicenter study included 3462 transarterial TAVR patients receiving newer generation devices. The patients were compared according to their NYHA class at 1 month of follow-up (NYHA I-II vs NYHA III-IV). A multivariate logistic regression was performed to identify the predictors of 30-day NYHA class III-IV. Patient survival was compared with the Kaplan-Meier method and factors associated with decreased survival were identified with Cox regression analysis., Results: The mean age of the study population was 80.3±7.3 years, with 47% of women, and a median Society of Thoracic Surgeons score of 3.8% [IQR, 2.5-5.8]. A total of 208 patients (6%) were in NYHA class III-IV 1 month after TAVR. Predictors of 30-day NYHA class III-IV were baseline NYHA class III-IV (OR, 1.76; 95%CI, 1.08-2.89; P=.02), chronic pulmonary obstructive disease (OR, 1.80; 95%CI, 1.13-2.83; P=.01), and post-TAVR severe mitral regurgitation (OR, 2.00; 95%CI, 1.21-3.31; P<.01). Patients in NYHA class III-IV 1 month after TAVR were at higher risk of death (HR, 3.68; 95%CI, 2.39-5.70; P<.01) and heart failure-related hospitalization (HR, 6.00; 95%CI, 3.76-9.60; P<.01) at 1-year follow-up., Conclusions: Up to 6% of contemporary TAVR patients exhibited an impaired functional status following TAVR. Worse baseline NYHA class, chronic pulmonary obstructive disease, and severe mitral regurgitation predicted 30-day NYHA class III/IV, and this determined a higher risk of mortality and heart failure hospitalization at 1-year follow-up. Further studies on the prevention and treatment optimization of patients with impaired functional status after TAVR are needed., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA., Methods: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes., Results: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P =0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P =1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P =0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P =0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P =0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P =0.80)., Conclusions: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445., Competing Interests: Disclosures Dr Rodés-Cabau has received institutional research grants from and is consultant for Edwards Lifesciences and Medtronic. Dr Ribeiro has received fees as a proctor from Medtronic, Edwards Lifesciences and Boston Scientific and research grant from Medtronic. Dr Al-Atassi has received honoraria/fees as a proctor from Edwards. Dr Nombela-Franco has received consulting fees from Edwards Lifesciences. Dr Conradi is a member of the Advisory Board of Medtronic, Abbott, and JenaValve; and has received consulting fees from Edwards Lifesciences, Boston Scientific, MicroPort, Venus Medtech, and PiCardia. Dr Moris received fees as a proctor from Medtronic and Boston Scientific. Dr Pibarot has received institutional research grants from Edwards Lifesciences, Medtronic, Pi-Cardia, and Novartis. The other authors report no conflicts.

The growing number of candidates for transcatheter aortic valve replacement (TAVR) has increased the interest in the concomitant presence of coronary artery disease (CAD) and severe aortic stenosis (AS), prompting the need to define the appropriate revascularization strategy for each case. The reported prevalence of concurrent AS and CAD has varied over the years on the basis of the CAD definition and the population evaluated. Revascularization for treating CAD in patients with severe AS involves additional interventions that could impact outcomes. The addition of coronary artery bypass grafting (CABG) to surgical aortic valve replacement (SAVR) has demonstrated favourable effects on long-term prognosis, while the impact of adding percutaneous coronary intervention (PCI) to TAVR may depend on the CAD complexity and the feasibility of achieving complete or reasonably incomplete revascularization. Furthermore, the comparison between SAVR+CABG and TAVR+PCI in low-intermediate surgical risk and low-intermediate complex CAD patients did not reveal differences in all-cause mortality or stroke between the groups. However, there is some evidence showing a lower incidence of major cardiovascular events with the SAVR+CABG strategy for patients with complex CAD. Thus, SAVR+CABG seems to be the best option for patients with low-intermediate surgical risk and complex CAD, and TAVR+PCI for high surgical risk patients seeking complete and/or reasonable incomplete revascularization. After deciding between TAVR+PCI or SAVR+CABG, factors such as timing for PCI, low ejection fraction, coronary reaccess, and valve durability must be considered. Finally, alternative methods for assessing CAD severity are currently under evaluation to ascertain their real value for guiding revascularization in patients with severe AS with CAD., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: To evaluate the prevalence, clinical characteristics, and outcomes of patients with angina undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis., Methods: A total of 1687 consecutive patients with severe aortic stenosis undergoing TAVR at our center were included and classified according to patient-reported angina symptoms prior to the TAVR procedure. Baseline, procedural and follow-up data were collected in a dedicated database., Results: A total of 497 patients (29%) had angina prior to the TAVR procedure. Patients with angina at baseline showed a worse New York Heart Association (NYHA) functional class (NYHA class> II: 69% vs 63%; P=.017), a higher rate of coronary artery disease (74% vs 56%; P <.001), and a lower rate of complete revascularization (70% vs 79%; P <.001). Angina at baseline had no impact on all-cause mortality (HR, 1.02; 95%CI, 0.71-1.48; P=.898) and cardiovascular mortality (HR, 1.2; 95%CI, 0.69-2.11; P=.517) at 1 year. However, persistent angina at 30 days post-TAVR was associated with increased all-cause mortality (HR, 4.86; 95%CI, 1.71-13.8; P=.003) and cardiovascular mortality (HR, 20.7; 95%CI, 3.50-122.6; P=.001) at 1-year follow-up., Conclusions: More than one-fourth of patients with severe aortic stenosis undergoing TAVR had angina prior to the procedure. Angina at baseline did not appear to be a sign of a more advanced valvular disease and had no prognostic impact; however, persistent angina at 30 days post-TAVR was associated with worse clinical outcomes., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Periprocedural myocardial infarction (MI) according to the Society for Cardiovascular Angiography and Interventions (SCAI) criteria has prognostic relevance among patients undergoing percutaneous coronary intervention (PCI). However, it is unclear whether the type of cardiac biomarker used for the diagnosis of periprocedural MI plays a role in terms of event frequency and outcomes., Objectives: To compare the characteristics of SCAI periprocedural MI based on creatine kinase-myocardial band fraction (CK-MB) vs. high-sensitivity cardiac troponin (hs-cTn) in patients undergoing elective PCI., Methods and Results: Between 2017 and 2021, periprocedural MI was assessed in a prospective study. The primary clinical outcome of interest was all-cause death at 1-year follow-up. A total of 1010 patients undergoing elective PCI were included. SCAI periprocedural MI based on CK-MB vs. hs-cTnI occurred in 1.8 and 13.5% of patients, respectively. hs-cTnI periprocedural MI in the absence of concomitant CK-MB criteria was associated with lower rates of ancillary criteria, including angiographic, ECG, and cardiac imaging criteria. At 1-year follow-up, periprocedural MI defined by CK-MB (adjusted hazard ratio, HR, 4.27, 95% confidence intervals, CI, 1.23-14.8; P = 0.022) but not hs-cTnI (adjusted HR 2.04, 95% CI 0.94-4.45; P = 0.072) was associated with a higher risk of all-cause death. Hs-cTnI periprocedural MI was not predictive of death unless accompanied by CK-MB criteria (adjusted HR 4.64, 95% CI 1.32-16.31; P = 0.017)., Conclusion: In the setting of elective PCI, using hs-cTn instead of CK-MB resulted in a substantial increase in SCAI periprocedural MI events, which were not prognostically relevant in the absence of concurrent CK-MB elevations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS., Study Design: PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry., Conclusions: The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The updated Valve Academic Research Consortium (VARC) definition for bleeding events after transcatheter aortic valve replacement (TAVR) lacks of clinical validation., Objectives: The aim of this study was to determine the incidence, predictors, and clinical impact of bleeding events following TAVR as defined by recent VARC-3 criteria., Methods: A total of 2,384 consecutive patients with severe symptomatic aortic stenosis undergoing TAVR were included. Early (at index hospitalization) and late (after hospital discharge) bleeding complications were defined according to VARC-3 criteria as type 1, 2, 3, or 4. Baseline, procedural, and follow-up (24 [IQR: 12-43] months) data were prospectively collected., Results: Bleeding events occurred in 761 patients (31.9%): types 1, 2, 3, and 4 in 169 (22.2%), 399 (52.4%), 149 (19.6%), and 44 (5.8%) patients, respectively. The primary vascular access site and gastrointestinal locations were the most common bleeding sources among early and late bleeding events, respectively. Female sex, thoracotomy access, larger (14-F) sheath use, and dual antiplatelet therapy determined an increased risk of early bleeding events (P < 0.02 for all). The use of the radial artery for secondary access was associated with a significant risk reduction of early bleeding (P < 0.001). Type 2 and type 3 events were associated with an increased mortality risk at 30-day (HR: 2.94 [95% CI: 1.43-6.03; P = 0.003] and HR: 4.91 [95% CI: 2.19-11.03; P < 0.001], respectively) and 1-year (HR: 1.86 [95% CI: 1.28-2.69; P = 0.001] and HR: 2.28 [95% CI: 1.41-3.66; P = 0.001], respectively) follow-up. A similar prognostic pattern was observed when applying VARC-2 criteria but with a much lower global incidence of early bleeding events (19% vs 27%; P < 0.001)., Conclusions: Bleeding events after TAVR were associated with poorer short- and long-term survival. The magnitude of this correlation was proportional to bleeding severity defined according to VARC-3 criteria. Further studies on bleeding prevention following TAVR are warranted to improve procedural safety and patient prognosis., Competing Interests: Funding Support and Author Disclosures Dr Real is supported by the Fundacion Interhospitalaria Para la Investigación Cardiovascular (Madrid, Spain). Dr Nuche is a recipient of a grant from Fundación Alfonso Martín Escudero (Madrid, Spain). Dr Rodés-Cabau has received institutional research grants and speaker and consultant fees from Edwards Lifesciences and Medtronic, and holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions (Laval University, Quebec City, Canada). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients undergoing percutaneous coronary intervention (PCI) in the work-up pre-transcatheter aortic valve replacement (TAVR), the incidence and clinical impact of late bleeding events (LBEs) remain largely unknown., Objectives: This study sought to determine the incidence, clinical characteristics, associated factors, and outcomes of LBEs in patients undergoing PCI in the work-up pre-TAVR., Methods: This was a multicenter study including 1,457 consecutive patients (mean age 81 ± 7 years; 41.5% women) who underwent TAVR and survived beyond 30 days. LBEs (>30 days post-TAVR) were defined according to the Valve Academic Research Consortium-2 criteria., Results: LBEs occurred in 116 (7.9%) patients after a median follow-up of 23 (IQR: 12-40) months. Late bleeding was minor, major, and life-threatening or disabling in 21 (18.1%), 63 (54.3%), and 32 (27.6%) patients, respectively. Periprocedural (<30 days post-TAVR) major bleeding and the combination of antiplatelet and anticoagulation therapy at discharge were independent factors associated with LBEs (P ≤ 0.02 for all). LBEs conveyed an increased mortality risk at 4-year follow-up compared with no bleeding (43.9% vs 36.0; P = 0.034). Also, LBE was identified as an independent predictor of all-cause mortality after TAVR (HR: 1.39; 95% CI: 1.05-1.83; P = 0.020)., Conclusions: In TAVR candidates with concomitant significant coronary artery disease requiring percutaneous treatment, LBEs after TAVR were frequent and associated with increased mortality. Combining antiplatelet and anticoagulation regimens and the occurrence of periprocedural bleeding determined an increased risk of LBEs. Preventive strategies should be pursued for preventing late bleeding after TAVR, and further studies are needed to provide more solid evidence on the most safe and effective antithrombotic regimen post-TAVR in this challenging group of patients., Competing Interests: Funding Support and Author Disclosures Dr Rodés-Cabau holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions (Laval University); and has received institutional research grants and speaker/consultant fees from Edwards Lifesciences and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the disease with a dismal impact on survival and quality of life. Several factors may derange the faint balance between left ventricular preload and afterload and precipitate the occurrence of symptoms and signs of acute heart failure (HF). A standardized approach for the management of this condition is currently lacking. Medical therapy finds very limited application in this setting, as drugs usually indicated for the control of acute HF might worsen hemodynamics in the presence of AS. Urgent aortic valve replacement is usually performed by transcatheter than surgical approach whereas, over the last decades, percutaneous balloon valvuloplasty gained renewed space as bridge to definitive therapy. This review focuses on the pathophysiological aspects of acute advanced AS and summarizes current evidence on its management., (© 2023. The Author(s).)

Objectives: Arterial hypertension is associated with the triggering of the renin-angiotensin system, leading to left ventricle fibrosis and worse cardiovascular outcomes. In this study, patients with comorbid arterial hypertension and severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) were selected from the EffecTAVI registry to evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on cardiovascular mortality., Methods: We enrolled 327 patients undergoing TAVI from the EffecTAVI registry. Using Kaplan-Meier event rates and study-stratified multivariable Cox proportional hazards regression models, we evaluated 2-year clinical outcomes according to the ACEI/ARB therapy status at enrollment., Results: Among the included patients, 222 (67.9%) were on ACEIs/ARBs at baseline, whereas 105 (32.1%) were not. Treatment with ACEIs/ARBs was significantly associated with a 2-year decrease in the rate of cardiovascular mortality (HR = 0.44, 95% CI: 0.23-0.81, p  = 0.009). This association remained stable after both multivariable adjustment and propensity score matching., Conclusion: In a cohort of hypertensive patients with severe AS who were selected from the EffecTAVI registry, ACEI/ARB treatment at baseline was found to be independently associated with a lower risk of 2-year cardiovascular mortality, suggesting a potential benefit of this treatment. More trials are needed to validate this finding and to understand the full benefit of this treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Basile, Mancusi, Franzone, Avvedimento, Bardi, Angellotti, Castiello, Mariani, Manzo, De Luca, Cirillo, De Simone and Esposito.)

Background: Limited data are available on the risk of periprocedural myocardial infarction (MI) in patients undergoing complex versus noncomplex percutaneous coronary intervention (PCI)., Methods: We assessed the risk of periprocedural MI according to the fourth Universal definition of myocardial infarction (UDMI) and several other criteria among patients undergoing elective PCI in a prospective, single-center registry. Complex PCI included at least one of the following: 3 coronary vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, treatment of chronic total occlusion, and use of rotational atherectomy., Results: Between 2017 and 2021, we included 1010 patients with chronic coronary syndrome, of whom 226 underwent complex PCI (22.4%). The rate of periprocedural MI according to the fourth UDMI was significantly higher in complex compared to noncomplex PCI patients (26.5% vs. 14.5%, p < 0.001). Additionally, periprocedural MI was higher in the complex PCI group using SCAI (4% vs. 1.1%, p = 0.009), ARC-2 (13.7% vs. 8.0%, p = 0.013), ISCHEMIA (5.8% vs. 1.7%, p = 0.002), and EXCEL criteria (4.9% vs. 2.0%, p = 0.032). SYNTAX periprocedural MI occurred at low rates in both groups (0.9% vs. 0.6%, p = 0.657). Complex PCI was an independent predictor of the fourth UDMI periprocedural MI (odds ratio [OR] 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.031)., Conclusions: In patients with chronic coronary syndrome undergoing elective PCI, complex PCI is associated with a significantly higher risk of periprocedural MI using multiple definitions. These findings highlight the importance of considering upfront this risk in the planning of complex PCI procedures., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Echocardiography represents the most important diagnostic tool in the evaluation of aortic stenosis. The echocardiographic assessment of its severity should always be performed through a standardized and stepwise approach in order to achieve a comprehensive evaluation. The latest technical innovations in the field of echocardiography have improved diagnostic accuracy, guaranteeing a better and more detailed evaluation of aortic valve anatomy. An early diagnosis is of utmost importance since it shortens treatment delays and improves patient outcomes. Echocardiography plays a key role also in the evaluation of all the structural changes related to aortic stenosis. Detailed evaluation of subtle and subclinical changes in left ventricle function has a prognostic significance: scientific efforts have been addressed to identify the most accurate global longitudinal strain cut-off value able to predict adverse outcomes. Moreover, in recent years the role of artificial intelligence is increasingly emerging as a promising tool able to assist cardiologists in aortic stenosis screening and diagnosis, especially by reducing the rate of aortic stenosis misdiagnosis.

Within the last two decades, transcatheter aortic valve replacement (TAVR) has transformed the treatment strategy for symptomatic severe aortic stenosis (AS), representing a less invasive alternative to traditional open-chest surgery. With time, advances in device features, imaging planning, and implantation techniques have contributed to an improvement in safety as well as a reduction in procedural complications. This has led to the expansion of TAVR to lower-risk patients, where TAVR has shown favorable outcomes compared to surgical aortic valve replacement (SAVR). As TAVR expands to younger and lower-risk patients with longer life expectancies, the need for reintervention for failing transcatheter heart valves is expected to increase. Redo-TAVR has gained increasing relevance in the lifetime management of AS as one of the treatment strategies available for structural valve dysfunction (SVD). However, some issues are associated with this approach, including coronary re-access and the risk of coronary obstruction. In this review, we provide essential concepts to properly select candidates for Redo-TAVR, updated data on clinical outcomes and complication rates, and current gaps in evidence.

Introduction: Small aortic annulus (SAA) poses a challenge in the management of patients with severe aortic stenosis requiring aortic valve replacement - both surgical and transcatheter - since it has been associated with worse clinical outcomes., Areas Covered: This review aims to comprehensively summarize the available evidence regarding the management of aortic stenosis in patients with SAA and discuss the current controversies as well as future perspectives in this field., Expert Opinion: It is paramount to agree in a common definition for diagnosing and properly treating SAA patients, and for that purpose, multidetector computer tomography is essential. The results of recent trials led to the expansion of transcatheter aortic valve replacement among patients of all the surgical-risk spectrum, and the choice of treatment (transcatheter, surgical) should be based on patient comorbidities, anatomical characteristics, and patient preferences.

Background: Although >150,000 mitral TEER procedures have been performed worldwide, the impact of MR etiology on MV surgery after TEER remains unknown., Objectives: The authors sought to compare outcomes of mitral valve (MV) surgery after failed transcatheter edge-to-edge repair (TEER) stratified by mitral regurgitation (MR) etiology., Methods: Data from the CUTTING-EDGE registry were retrospectively analyzed. Surgeries were stratified by MR etiology: primary (PMR) and secondary (SMR). MVARC (Mitral Valve Academic Research Consortium) outcomes at 30 days and 1 year were evaluated. Median follow-up was 9.1 months (IQR: 1.1-25.8 months) after surgery., Results: From July 2009 to July 2020, 330 patients underwent MV surgery after TEER, of which 47% had PMR and 53.0% had SMR. Mean age was 73.8 ± 10.1 years, median STS risk at initial TEER was 4.0% (IQR: 2.2%-7.3%). Compared with PMR, SMR had a higher EuroSCORE, more comorbidities, lower LVEF pre-TEER and presurgery (all P < 0.05). SMR patients had more aborted TEER (25.7% vs 16.3%; P = 0.043), more surgery for mitral stenosis after TEER (19.4% vs 9.0%; P = 0.008), and fewer MV repairs (4.0% vs 11.0%; P = 0.019). Thirty-day mortality was numerically higher in SMR (20.4% vs 12.7%; P = 0.072), with an observed-to-expected ratio of 3.6 (95% CI: 1.9-5.3) overall, 2.6 (95% CI: 1.2-4.0) in PMR, and 4.6 (95% CI: 2.6-6.6) in SMR. SMR had significantly higher 1-year mortality (38.3% vs 23.2%; P = 0.019). On Kaplan-Meier analysis, the actuarial estimates of cumulative survival were significantly lower in SMR at 1 and 3 years., Conclusions: The risk of MV surgery after TEER is nontrivial, with higher mortality after surgery, especially in SMR patients. These findings provide valuable data for further research to improve these outcomes., Competing Interests: Funding Support and Author Disclosures Dr Bhadra has received travel compensation from Edwards Lifesciences. Dr Tagliari has received research support from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Dr Leurent has been a consultant and physician proctor for and has received speaker honoraria from Abbott. Dr Asgar has been a consultant for Medtronic, Abbott, Edwards Lifesciences, and W. L. Gore & Associates; and has received research grants from Abbott. Dr Leroux has been a physician proctor for Medtronic and Abbott; and a consultant for Edwards Lifesciences. Dr Dumonteil has received speaker honoraria and travel reimbursement by Edwards Lifesciences; and has been a physician proctor and consultant for Edwards Lifesciences. Dr Geirsson has been a member of the Medtronic Strategic Surgical Advisory Board. Dr Wyler von Ballmoos has served as a consultant for LivaNova, Medtronic, and Boston Scientific. Dr Reardon has been a consultant for Medtronic, Boston Scientific, Abbott, and W. L. Gore & Associates. Dr Bapat has served as a consultant for Medtronic, Edwards Lifesciences, 4C Medical, and Boston Scientific. Dr Nazif has equity in Venus Medtech; and has received consulting fees or honoraria from Keystone Heart, Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Kaneko has been a speaker for Edwards Lifesciences, Medtronic, Abbott, and Baylis Medical; and has been a consultant for 4C Medical. Dr Modine has been a physician proctor and consultant for Medtronic, Edwards Lifesciences, and Abbott. Dr Denti has received speaker honoraria from Abbott and Edwards Lifesciences; and has been a consultant for InnovHeart. Dr Tang has been a physician proctor for Medtronic; a consultant for Medtronic, Abbott, and NeoChord; and a physician advisory board member for Abbott, Boston Scientific and JenaValve; and has received speaker honoraria from Siemens Healthineers and East End Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Valve Academic Research Consortium (VARC)-3 definition for myocardial injury after transcatheter aortic valve replacement (TAVR) lacks of clinical validation., Objectives: This study sought to determine the incidence, predictors, and clinical impact of periprocedural myocardial injury (PPMI) following TAVR as defined by recent VARC-3 criteria., Methods: We included 1,394 consecutive patients who underwent TAVR with a new-generation transcatheter heart valve. High-sensitivity troponin levels were assessed at baseline and within 24 hours after the procedure. PPMI was defined according to VARC-3 criteria as an increase ≥70 times in troponin levels (vs ≥15 times according to the VARC-2 definition). Baseline, procedural, and follow-up data were prospectively collected., Results: PPMI was diagnosed in 193 (14.0%) patients. Female sex and peripheral artery disease were independent predictors of PPMI (P < 0.01 for both). PPMI was associated with a higher risk of mortality at 30-day (HR: 2.69, 95% CI: 1.50-4.82; P = 0.001) and 1-year (for all-cause mortality, HR: 1.54; 95% CI: 1.04-2.27; P = 0.032; for cardiovascular mortality, HR: 3.04; 95% CI: 1.68-5.50; P < 0.001) follow-up. PPMI according to VARC-2 criteria had no impact on mortality., Conclusions: About 1 out of 10 patients undergoing TAVR in the contemporary era had PPMI as defined by recent VARC-3 criteria, and baseline factors like female sex and peripheral artery disease determined an increased risk. PPMI had a negative impact on early and late survival. Further studies on the prevention of PPMI post-TAVR and implementing measures to improve outcomes in PPMI patients are warranted., Competing Interests: Funding Support and Author Disclosures Dr Real was funded by the Fundación Interhospitalaria para la Investigación Cardiovascular. Dr Nuche was the recipient of a grant from the Fundación Alfonso Martín Escudero (Madrid, Spain). Dr Rodés-Cabau has received institutional research grants and speaker/consultant fees from Edwards Lifesciences and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Transcatheter aortic valve implantation (TAVI) is a widely adopted treatment option for patients with severe aortic stenosis. Its popularity has grown significantly in recent years due to advancements in technology and imaging. As TAVI use is increasingly expanded to younger patients, the need for long-term assessment and durability becomes paramount. This review aims to provide an overview of the diagnostic tools to evaluate the hemodynamic performance of aortic prosthesis, with a special focus on the comparison between transcatheter and surgical aortic valves and between self-expandable and balloon-expandable valves. Moreover, the discussion will encompass how cardiovascular imaging can effectively detect long-term structural valve deterioration.

Advances in technology and imaging have expanded the range of tools for diagnosing aortic stenosis (AS). The accurate assessment of aortic valve area and mean pressure gradient is crucial to determine which patients are appropriate candidates for aortic valve replacement. Nowadays, these values can be obtained noninvasively or invasively, with similar results. Contrariwise, in the past, cardiac catheterization played a major role in the evaluation of AS severity. In this review, we will discuss the historical role of the invasive assessment of AS. Moreover, we will specifically focus on tips and tricks for properly performing cardiac catheterization in patients with AS. We will also elucidate the role of invasive methods in current clinical practice and their additional value to the information provided through non-invasive techniques.

Transcatheter aortic valve implantation (TAVI) is an increasingly popular treatment option for patients with severe aortic stenosis. Recent advancements in technology and imaging tools have significantly contributed to the success of TAVI procedures. Echocardiography plays a pivotal role in the evaluation of TAVI patients, both before and after the procedure. This review aims to provide an overview of the most recent technical advancements in echocardiography and their use in the follow-up of TAVI patients. In particular, the focus will be on the examination of the influence of TAVI on left and right ventricular function, which is frequently accompanied by other structural and functional alterations. Echocardiography has proven to be key also in detecting valve deterioration during extended follow-up. This review will provide valuable insights into the technical advancements in echocardiography and their role in the follow-up of TAVI patients.

Patients with peripheral artery disease (PAD) are at an increased risk of major adverse cardiovascular events, and those with disease in the lower extremities are at risk of major adverse limb events primarily driven by atherothrombosis. Traditionally, PAD refers to diseases of the arteries outside of the coronary circulation, including carotid, visceral and lower extremity peripheral artery disease, and the heterogeneity of PAD patients is represented by different atherothrombotic pathophysiology, clinical features and related antithrombotic strategies. The risk in this diverse population includes systemic risk of cardiovascular events as well as risk related to the diseased territory (e.g., artery to artery embolic stroke for patients with carotid disease, lower extremity artery to artery embolism and atherothrombosis in patients with lower extremity disease). Moreover, until the last decade, clinical data on antithrombotic management of PAD patients have been drawn from subanalyses of randomized clinical trials addressing patients affected by coronary artery disease. The high prevalence and related poor prognosis in PAD patients highlight the pivotal role of tailored antithrombotic therapy in patients affected by cerebrovascular, aortic and lower extremity peripheral artery disease. Thus, the proper assessment of thrombotic and hemorrhagic risk in patients with PAD represents a key clinical challenge that must be met to permit the optimal antithrombotic prescription for the various clinical settings in daily practice. The aim of this updated review is to analyze different features of atherothrombotic disease as well as current evidence of antithrombotic management in asymptomatic and secondary prevention in PAD patients according to each arterial bed.